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2,3-Diethyl-5-methylpyrazine (DEMP) is recognized for its unique nutty scent but faces limitations due to rapid evaporation. The primary objective of this study was to explore the effect of incorporating DEMP with β-cyclodextrin (β-CD) and chitosan (CS) as wall material on the microstructure and thermal release behavior, antibacterial, and antioxidant characteristics. Initially, the microcapsules preparation process underwent optimization with embedding rate of 78.03 % through response surface by ultrasonic technique. The characterization of microcapsules was confirmed through SEM, FT-IR and TEM, with the majority exhibiting smooth and shell core structures that overlapped. Through sustained release kinetics analysis, the release of microcapsules under 80 °C, 50 °C and room temperature was more in line with the first-order kinetic and Avrami kinetic equation. The heat release kinetics analysis yielded a well-matched linear fitting curve. Additionally, microcapsules effectively suppressed the growth of S. aureus and E. coli germs, and demonstrated strong antioxidant properties, compared with DEMP. Adding 10 mg microcapsules to the Heat Not Burning (HNB) cigarette, the sensory quality was significantly improved. This discovery has the potential to pave a new route for the encapsulation of fragrance molecules, and expanding their multifunctional usages for enhancing the flavor of cigarettes and food., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors to be published., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: In Mongolian medicine, Loulu flower (LLF), the dried inflorescence of Rhaponticum uniflorum (L.) DC. from the Compositae family, has been used to clear heat and relieve toxicity for millennia, particularly in the treatment of pneumonia., Aim of This Study: To reveal the effects of LLF on mice with lipopolysaccharide (LPS)-stimulated acute lung injury (ALI) and elucidate the underlying mechanisms., Materials and Methods: ALI was established in BALB/c mice via nasal drops administration of LPS (5 mg/kg). The mice were then orally administrated with various doses of LLF extracts and the positive drug dexamethasone (DEX, 5 mg/kg), once daily for seven consecutive days. Last day, after being stimulated with LPS for 6h, the mice were closed dislocation of cervical vertebra, the serum, bronchus alveolar lavage fluid (BALF) and lung tissue were put into the EP tube and stored at -80 °C for further analysis. The changes of histopathology were tested by hematoxylin and eosin stain (H&E), the levels of, IL-1β, IL-18, TNF-α and IL-4 in BALF and serum were measured by ELISA. The pathways related to the treatment of ALI were predicted by network pharmacology. The expression levels of TLR4/NF-κB and NLRP3 signaling pathway-associated proteins, COX-2 and ERK were tested by western blotting. The levels of P65 and NLRP3 in lung tissues were determined by immunofluorescence analysis., Results: LLF total extract and the extract parts could alleviate the inflammatory cell infiltration, thicken the alveolar walls in lung tissues, reduce the levels of IL-18, IL-1β in BALF, the TNF-α in both BALF and serum, meantime enhance the level of IL-4 in BALF and serum in mice with LPS-induced ALI. Our network pharmacology and comprehensive gene ontology analyses revealed the active constituents of LLF and the pathways, including TLR4/NF-κB, NLRP3 and MAPK signaling pathways, which play significant roles in ALI. Furthermore, both the total extract and its extraction portions suppressed the expressions of proteins related with the COX-2, p-ERK and TLR4/NF-κB signaling pathway (TLR4, p-IκB, p-p65), as well as the NLRP3 signaling pathway (NLRP3, cleaved caspase-1, caspase-1, IL-1β)., Conclusion: LLF could improve the pathological changes and reducing inflammatory reactions in mice induced by LPS. The mechanism may be related to the modulation of the TLR4/NLRP3 signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/H 2 S cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/H 2 S cross-talk and revealing the role of HNO in plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Adolescents with secondary hyperaldosteronism often present with severe and treatment-resistant hypertension, along with hypokalemia. Renovascular hypertension is frequently caused by renal artery stenosis, primarily due to atherosclerosis and fibromuscular dysplasia (FMD). The presence of an accessory renal artery (ARA) is a common anatomical variation that can contribute to secondary renal vascular hypertension. However, FMD occurring in the ARA is a rare cause of renal vascular hypertension. Juxtaglomerular cell tumor (JGCT) represents a rare etiology of renal hypertension. The co-occurrence of the pathogenic ARA with JGCT is infrequently reported in the existing literature., Case Presentations: This case study presents a young individual with a 12-year history of resistant hypertension, initially diagnosed with pathogenic ARA but later confirmed as JGCT 4 years later. Following surgery for JGCT, the patient experienced only temporary stabilization of blood pressure without anti-hypertensive medication. Stenosis of the ARA was definitively diagnosed one and a half years post-surgery, with FMD occurring on the ARA strongly suspected. The patient underwent balloon dilatation angioplasty 3 years later, leading to sustained blood pressure stability with the use of two medications., Conclusions: The case study discussed herein involves a patient with resistant hypertension initially diagnosed with ARA but later determined to have late-onset JGCT and renal artery stenosis. It is imperative to consider atypical JGCT in young patients exhibiting resistant hypertension, hypokalemia, and hyperreninemia. Adequate management of renal artery stenosis is crucial in the management of hyperreninemic hypertension., Competing Interests: Declarations Ethics approval and consent to participate All procedures were conducted in compliance with the ethical regulations established by the committees of Guangzhou Red Cross Hospital. Consent for publication Written informed consent for publication of the clinical details and images was obtained from the patient. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

Background: Evaluate imaging photoplethysmography (iPPG) as a novel noninvasive technique to assess flap perfusion in head and neck free flap reconstructive (FFR) surgeries., Methods: Intraoperative iPPG was performed in 17 patients undergoing FFR surgery. Imaging consisted of a 30-s video from which perfusion maps were extracted, providing detailed information about blood flow and pulsatility in the flap microvasculature. During each procedure, iPPG acquisitions were acquired representing distinct perfusion conditions of the flap (fully perfused/ischemic/reperfused). When possible, postoperative measurements were performed to assess flap recovery during the critical time period (3 days) and long-term follow-up (30 days)., Results: Perfusion maps, displaying iPPG amplitude and delay times, correlated strongly (p < 0.001) with the perfusion status of the tissue. One case of postoperative thrombosis, leading to flap failure, was identified with iPPG. After surgical revision in this case, flap perfusion was restored and confirmed by iPPG. Postoperative follow-up imaging allowed for objective visualization of flap recovery short term (3 days) and up to 30 days after the surgical procedure., Conclusions: This study shows that iPPG is suitable for objective and noninvasive assessment of flap perfusion in head and neck FFR surgery. In addition, postoperative monitoring shows potential for assessing flap perfusion in patients with increased risk of postoperative complications., (© 2024 The Author(s). Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

This study investigated the impact of chlorine dioxide (ClO 2 ) treatment on the storage quality of Toona sinensis after harvesting. Toona sinensis samples treated with different concentrations (0.2, 0.4, 0.8, 1.6 mg/L) of chlorine dioxide and stored at (4 ± 1) °C, with sampling test every 2 nd day. The changes in sensory, nutritional, and chlorine dioxide residues of T. sinensis were checked regularly. Results revealed that moderate (0.4~0.8 mg/L) chlorine dioxide concentrations maintained sensory quality, inhibited T. sinensis weight loss, slowed flavonoid and vitamin C content depletion, reduced nitrite content, and enhanced superoxide dismutase activity. The chlorine dioxide resides in T. sinensis were below the national standards (<2.0 mg/kg; GB 5009.244-2016). Overall, 0.4~0.8 mg/L chlorine dioxide treatment showed optimal effects on T. sinensis , providing a scientific basis for extended storage and preservation of T. sinensis ., Competing Interests: The authors declare that they have no competing interests. Yunhong Gao is the legal representative of the Sichuan Yizhong Agricultural Development Company., (© 2024 Zeng et al.)

Background and Purpose: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is an index that may provide insights into intracranial waste clearance processes. Glymphatic system dysfunction has been suggested to play a role in the development of major depressive disorder (MDD). Additionally, fatigue-a common precursor of MDD-is also closely connected to the waste clearance function of the central nervous system (CNS), further underscoring the significance of efficient waste removal in MDD. However, evidence linking altered DTI-ALPS index to MDD remains limited. This study aims to investigate the changes in the DTI-ALPS index in patients with MDD and explore the potential interplay between DTI-ALPS index alterations, fatigue, and the presence of MDD., Material and Methods: A total of 46 patients with MDD and 55 healthy controls (HC) were included in the study. All participants underwent diffusion tensor imaging using the same 3-T MRI (3-Tesla Magnetic Resonance Imaging) scanner. The DTI-ALPS index was assessed, and the Chalder Fatigue Scale (CFS) was used to evaluate fatigue levels in both groups, and the 17-item Hamilton Depression Rating Scale (HAMD-17) was used to evaluate the severity of depression in the patients. We compared the DTI-ALPS index and clinical characteristics between the MDD and HC group, and explored the relationship among the DTI-ALPS index, CFS scores, and the presence of MDD through mediation analysis., Results: The DTI-ALPS index in the right hemisphere (DTI-ALPS-R) is significantly lower in patients with MDD (t = 2.41, P = 0.02). The MDD patients exhibited significantly higher scores on the CFS scales compared with HCs (t = 13.12, P <.001). Mediation analysis showed that the CFS score plays a significant mediating role between DTI-ALPS-R and the presence of MDD, acting as a full mediator (indirect effect β = -0.230, 95 % CI: [-0.388, -0.059])., Conclusion: Our study found that patients with MDD have a reduced DTI-ALPS index. This reduction appears to contribute to the development of MDD by facilitating the accumulation of fatigue symptoms. These findings may provide a new perspective on the pathogenesis of MDD, suggest a potential new biomarker for MDD, and offer new insights for its treatment., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Curcumae Rhizoma (CR) is a traditional Chinese medicine used frequently in clinics, which contains volatile components that exhibit various active effects. This study explores the effect of Curcumae Rhizoma volatile oil (CRVO) on depressive mice and its possible mechanism of action., Methods: Chemical composition of CRVO was analysed by GC-MS. DPPH and ABTS free radical scavenging assays were used to evaluate the in vitro antioxidant capacity of CRVO. A chronic unpredictable mild stress (CUMS) model was used to evaluate the antidepressant effect of CRVO. The effects of CRVO on oxidative stress in vivo were investigated using Nissl staining, ELISA and transmission electron microscopy. The Nrf2/HO-1/NQO1 signalling pathway was detected by western blotting and immunofluorescence. ML385, a Nrf2 inhibitor was used to validate the effect of Nrf2 on CUMS mice with CRVO treatment., Key Findings: Phytochemical analysis showed that CRVO is rich in its characteristic components, including curzerene (31.1%), curdione (30.56%), and germacrone (12.44%). In vivo, the administration of CRVO significantly ameliorated CUMS-induced depressive-like behaviours. In addition, inhalation of CRVO significantly alleviated the oxidative stress caused by CUMS and improved neuronal damage and mitochondrial dysfunction. The results of mechanistic studies showed that the mechanism of action is related to the Nrf2/HO-1/NQO1 pathway and the antioxidant and antidepressant effects of CRVO were weakened when ML385 was used., Conclusions: In summary, by regulating the Nrf2 pathway, inhalation of CRVO can reduce oxidative stress in depressed mice, thereby reducing neuronal damage and mitochondrial dysfunction to alleviate depression-like behaviours. Our study offers a prospective research foundation to meet the diversity of clinical medication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Low molecular weight polysaccharides had higher bio-activity and bioavailability compared to ultra-high molecular weight polysaccharides, this study aimed to obtain low molecular weight polysaccharides from Tremella fuciformis (TFLP) by using high-temperature and high-pressure assisted hydrochloric acid method to degrade Tremella fuciformis polysaccharides (TFP), and the structural characteristics, in vivo antioxidant and immune enhancing activities of TFP and TFLP was explored through Caenorhabditis elegans (C. elegans) and mice model. It was found that TFP and TFLP were acidic polysaccharides with molecular weights of 2238 kDa and 3 kDa, respectively. The glycosidic bonding of TFP and TFLP was mainly composed of different configurations of mannopyranose. TFP and TFLP had excellent in vivo antioxidant activity and stress resistance by regulating the mRNA transcription level and metabolites in C. elegans. Results also showed that TFP and TFLP could enhance the antioxidant capacity and immunity of serum, spleen and small intestine tissues in normal mice and cyclophosphamide-induced immunosuppressive mice through regulating the relative transcription and expression levels of anti-inflammatory related signaling factors, and it has found that TFLP showed better immune enhancement and antioxidant activity than TFP. In addition, Akkermansia, Bacteroides and Alloprevotella were characteristic bacteria at the genus level in immunosuppressed mice intervened with TFLP, with a significant increase in relative abundance. The content of SCFAs significantly increased in immunosuppressed mice by TFLP. These results indicated that TFP and TFLP had potential in vivo antioxidant and immune enhancing activities., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p < 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p < 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have nothing to disclose, except for the disclosure from following authors. Dr. Abecasis reports grants from National Heart Lung and Blood Institute (NIH), during the conduct of the study; personal fees and other from Regeneron Pharmaceuticals, outside the submitted work; Dr. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; outside the submitted work., (Copyright © 2024 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Metal-organic frameworks (MOFs), especially bimetallic MOFs, have attracted widespread attention for simulating the structure and function of natural enzymes. In this study, different morphologies of bimetallic Cu-Zn-MOF with different peroxidase (POD)-like activities were prepared by simply controlling the molar ratio of Cu 2+ and Zn 2+ . Among them, the doughnut-shaped Cu 9 -Zn 1 -MOF exhibited the largest POD-like activity. Cu 9 -Zn 1 -MOF was combined with glucose oxidase to construct a sensitive and selective glucose colorimetric biosensor with a linear detection range of 10-300 μM and a detection limit of 7.1 μm. Furthermore, Cu 9 -Zn 1 -MOF can efficiently convert hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals that effectively kill both gram-negative and gram-positive bacteria at low H 2 O 2 level. The results of this study may promote the synthesis of bimetallic MOFs and broaden their applications in the biomedical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread presence of antibiotics in aquatic environments, resulting from excessive use and accumulation, has raised significant concerns. A NiFe₂O₄/ZnIn₂S₄/Biochar (NFO/ZIS/BC) magnetic nanocomposite was successfully synthesized, demonstrating significantly enhanced electron-hole separation properties. Comprehensive investigations were conducted to evaluate the impact of various parameters, including catalyst mass, pH, and the presence of co-existing ions on the composite's performance. The nanoparticles of NiFe₂O₄ (NFO) and ZnIn₂S₄ (ZIS) were found to improve the surface stability and sulfamethoxazole removal capabilities of porous biochar, while also demonstrating high total organic carbon removal efficiencies. •O₂⁻ and h⁺ were identified as the predominant reactive oxygen species (ROS) in NFO/ZIS/BC-4 during the degradation process. The degradation outcomes of sulfamethoxazole under natural sunlight and water conditions were consistent with laboratory findings, affirming the robust applicative potential of NFO/ZIS/BC. Density functional theory (DFT) calculations were performed to elucidate the photocatalytic mechanism and identify potential intermediate products. Additionally, the types of heterojunctions present in the system were characterized and discussed. After multiple iterations, NFO/ZIS/BC-4 maintained effective photodegradation capabilities through five cycles. This study presents an effective method for the treatment of antibiotics in aquatic environments, offering significant potential for environmental applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Previous studies suggest a role for inflammation in hepatocarcinogenesis. However, no study has comprehensively evaluated associations between circulating inflammatory proteins and risk of hepatocellular carcinoma (HCC) among the general population. We conducted a nested case-control study in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) with 56 pairs of incident HCC cases and controls. External validation was performed in the UK Biobank (34 HCC cases and 48,471 non-HCC controls). Inflammatory protein levels were measured in pre-diagnostic plasma using the Olink® Inflammation Panel. We used conditional logistic regression to calculate multivariable odds ratios (ORs) with 95% confidence intervals (CIs) for associations between a 1-standard deviation (SD) increase in biomarker levels and HCC risk, considering a statistically significant threshold of false discovery rate (FDR)-adjusted p < .05. In the NHS/HPFS, among 70 analyzed proteins with call rates >80%, 15 proteins had significant associations with HCC risk (p FDR  < .05). Two proteins (stem cell factor, OR per SD  = 0.31, 95% CI = 0.16-0.58; tumor necrosis factor superfamily member 12, OR per SD  = 0.51, 95% CI = 0.31-0.85) were inversely associated whereas 13 proteins were positively associated with risk of HCC; positive ORs per SD ranged from 1.73 for interleukin (IL)-10 to 2.35 for C-C motif chemokine-19. A total of 11 proteins were further replicated in the UK Biobank. Seven of the eight selected positively associated proteins also showed positive associations with HCC risk by enzyme-linked immunosorbent assay, with ORs ranging from 1.56 for IL-10 to 2.72 for hepatocyte growth factor. More studies are warranted to further investigate the roles of these observed inflammatory proteins in HCC etiology, early detection, risk stratification, and disease treatment., (© 2024 UICC.)

Objectives: To evaluate whether the timing of initial antibiotic administration in patients with sepsis in hospital affects mortality., Methods: This systematic review and meta-analysis included studies from inception up to 19 May 2022. Interventional and observational studies including adult human patients with suspected or confirmed sepsis and reported time of antibiotic administration with mortality were included. Data were extracted by two independent reviewers. Summary estimates were calculated by using random-effects model. The primary outcome was mortality., Results: We included 42 studies comprising 190,896 patients with sepsis. Pooled data showed that the OR for patient mortality who received antibiotics ≤1 hr was 0.83 (95 %CI: 0.67 to 1.04) when compared with patients who received antibiotics >1hr. Significant reductions in the risk of death in patients with earlier antibiotic administration were observed in patients ≤3 hrs versus >3 hrs (OR: 0.80, 95 %CI: 0.68 to 0.94) and ≤6 hrs vs 6 hrs (OR: 0.57, 95 %CI: 0.39 to 0.82)., Conclusions: Our findings show an improvement in mortality in sepsis patients with early administration of antibiotics at <3 and <6 hrs. Thus, these results suggest that antibiotics should be administered within 3 hrs of sepsis recognition or ED arrival regardless of the presence or absence of shock., Competing Interests: Declaration of competing interest We declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The dysfunction of the ubiquitin-proteasome system (UPS) facilitates the malignant progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy has been proposed, identifying effective targets has been challenging. In this study, we conducted a focused screen of siRNA libraries targeting UPS-related WD40 repeat (WDR) proteins and found that silencing WDR20, a deubiquitinating enzyme activating factor, selectively inhibited the proliferation of HCC cells without affecting normal hepatocytes. Moreover, the downregulation of WDR20 expression induced HCC cellular senescence and suppressed tumor progression in xenograft, sleeping beauty transposon/transposase, and hydrodynamic tail vein injection-induced HCC models, and Alb-Cre + / MYC + HCC transgenic mouse models. Mechanistically, we found that WDR20 silencing disturbed the protein stability of c-Myc, orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc, thereby promoting the transcriptional activation of CDKN1A . Further investigation revealed a positive coexpression of WDR20 and c-Myc in a tissue microarray with 88 HCC clinical samples. By employing three patient-derived organoids from individuals with HCC, we have validated the decrease in c-Myc expression and the significant induction of senescence and growth inhibition following silencing of WDR20. This study not only uncovers the biological function of WDR20 and elucidates the molecular mechanism underlying its negative regulation of HCC cellular senescence but also highlight the potential of WDR20 as a promising target for HCC therapy., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Type 2 diabetes mellitus (T2DM) is a common complex metabolic disorder that exhibits a strong genetic predisposition. 5,10-methylenetetrahydrofolate reductase (MTHFR) regulates folate metabolism, which has been proposed to be associated with T2DM, although the relationship is inconsistent among different geographical areas. This study aimed to investigate the effects of MTHFR C677T (rs1801133) and A1298C (rs1801131) loci polymorphisms on T2DM susceptibility in the population of the Dali area in Yunnan Province, China., Methods: This case-control study included 445 patients with T2DM and 272 healthy control individuals from the Dali area of Yunnan Province. Genotyping of the MTHFR gene polymorphisms was performed using the competitive allele-specific PCR (KASP) method. The effects of genetic variations of the MTHFR gene on T2DM risk were evaluated using odds ratios (OR) and 95% confidence intervals., Results: The results of the present study revealed that the TT genotype (OR = 1.750, P = 0.030) and the T allele (OR = 1.252, P  = 0.047) at the MTHFR C677T locus were considerably associated with the increased odds of developing T2DM. In addition, the CC genotype (OR = 3.132, P  = 0.032) at the MTHFR A1298C locus also substantially increased the odds of developing T2DM. The T-A haplotype (OR = 1.305, P  = 0.030) of MTHFR C677T and A1298C exhibited the increased odds of developing T2DM. Biochemical index analyses showed that patients with T2DM who carried the CT or TT genotype of MTHFR C677T expressed substantially higher levels of fasting blood glucose (FBG), homocysteine (Hcy), and tumor necrosis factor-alpha (TNF- α ) than those of the CC genotype. Moreover, the FBG and Hcy levels were considerably higher in patients with T2DM who carried the CC or AC genotype of MTHFR A1298C than those of the AA genotype. No obvious association was observed between these MTHFR polymorphisms and cardiovascular risk in T2DM., Conclusion: Our study suggests that the genetic variations of MTHFR C677T and A1298C are significantly associated with T2DM susceptibility in the population of the Dali area of Yunnan Province, China., Competing Interests: The authors declare there are no competing interests., (©2024 Liu et al.)

A series of ester derivatives with hydroxyl groups were created by esterification of 1,2-propanediol and glycerol with o -toluoyl chloride via the catalyst 4-dimethylaminopyridine (DMAP). All the compounds were verified using nuclear magnetic resonance ( 1 H NMR, 13 C NMR), infrared spectroscopy, and high resolution mass spectrometry. Moisture absorption and desorption experiments were carried out on the compounds' pure systems and their systems in reconstituted tobacco, while their hygroscopicity and moisturizing properties were evaluated using low-field nuclear magnetic resonance imaging. Two compounds with better absorption and moisture retention were selected: 4 (1-hydroxypropan-2-yl 2-methylbenzoate) and 6 (2,3-dihydroxypropyl 2-methylbenzoate), respectively. Moreover, the thermal stability of compounds 4 and 6 were investigated using thermogravimetric (TG) analysis. The results of TG-DTG showed that the maximum mass loss rate of compound 4 appeared at 251.67 °C, with a mass loss rate of 87.61%. At the peak temperature of 291.83 °C, 6 showed the highest decomposition rate with 49.23% mass loss rate. To explore the antioxidant properties, we constructed three different antioxidant systems. Furthermore, compound 6 showed excellent effects, with scavenging rates reaching 69.28%, 71.92%, and 75.93%, respectively. Smoke volume results indicated that the compounds optimally replaced propanediol and glycerol at a rate of 40%. The results provide a theoretical reference for the development of new moisturizing agents based on polyol esters in the tobacco industry., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Species of the genus Eimeria cause coccidiosis in chickens, resulting in a huge burden to the poultry industry worldwide. Eimeria tenella is one of the most prevalent chicken coccidia in China, and E. tenella infection causes hemorrhagic cecitis., Methods: Using an established model of coccidiosis in chickens combined with necropsy, imaging of pathological tissue sections, and other techniques, we evaluated the gross and microscopic lesions of cecal tissue within 15 days after inoculation with sporulated oocysts and described the endogenetic developmental process and relationship between E. tenella infection and enteritis development in chickens., Results: We observed three generations of merogony and gamogony in E. tenella. We observed gross lesions in the cecum from 84 hpi (hours post inoculation) and microscopic lesions from 60 hpi. The lesions in the cecum mainly exhibited hemorrhagic enteritis. Their severity increased with the onset of the second generation of merogony. The lesions began to alleviate by the end of the endogenous stages of E. tenella., Conclusion: We show, for the first time, the complete observation of a series of changes in enteritis caused by 5 × 10 3 E. tenella oocysts. This study provides reference materials for E. tenella research and pathological diagnosis., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: The cardiometabolic index (CMI) has emerged as a novel marker for evaluating the distribution and dysfunction of visceral adipose tissue, yet its correlation with numerous diseases, particularly new-onset chronic conditions, remains underexplored. Therefore, we aim to explore the association of cardiometabolic index (CMI) and new-onset chronic diseases., Methods: The analysis utilized data from the China Health and Retirement Longitudinal Study, with a baseline in 2011 and follow-ups biennially until 2020. Fourteen new-onset chronic diseases were diagnosed based on self-report, and separate cohorts were created for each disease. CMI was calculated as triglycerides/high-density lipoprotein cholesterol multiplied by the waist-to-height ratio. Cox proportional hazards models were used to assess the association between CMI and new-onset chronic diseases, while restricted cubic spline (RCS) models were employed to explore potential nonlinear effects. Additional and sensitivity analyses included Kaplan-Meier survival curves, subgroup analyses, multiple imputations, and exclude outcome events at the first follow-up., Results: Higher levels of CMI were associated with an increased risk of new-onset hypertension (HR=1.05, 95% CI=1.04-1.06, P <0.001), diabetes (HR=1.08, 95% CI=1.06-1.09, P <0.001), dyslipidemia (HR=1.07, 95% CI=1.06-1.09, P <0.001), liver disease (HR=1.05, 95% CI=1.03-1.07, P <0.003), and stroke (HR=1.04, 95% CI=1.02-1.06, P <0.001), although the association with stroke was not significant after adjusting for confounders (HR=1.02, 95% CI=1.00-1.05, P =0.054). Participants in the highest quartile of CMI had a significantly higher risk of these diseases compared to those in the lowest quartile. RCS analyses showed a significant nonlinear relationship between CMI and the risk of these diseases above., Conclusions: CMI showed a significant positive association with the risk of new-onset chronic diseases such as hypertension, diabetes, dyslipidemia, and liver disease. Future applications of CMI hold promise as an effective marker for early identification of chronic disease risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhuo, Lai, Wan, Zhang and Chen.)

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent subtype of malignant renal cell carcinoma and is well known as a common genitourinary cancer. Stratifying tumors based on heterogeneity is essential for better treatment options. Methods: In this study, consensus clusters were constructed based on gene expression, DNA methylation, and gene mutation data, which were combined with multiple clustering algorithms. After identifying two heterogeneous subtypes, we analyzed the molecular characteristics, immunotherapy response, and drug sensitivity differences of each subtype. And we further integrated bulk data and single-cell RNA sequencing (scRNA-Seq) data to infer the immune cell composition and malignant tumor cell proportion of subtype-related cell subpopulations. Results: Among the two identified consensus subtypes (CS1 and CS2), CS1 was enriched in more inflammation-related and oncogenic pathways than CS2. Simultaneously, CS1 showed a worse prognosis and we found more copy number variations and BAP1 mutations in CS1. Although CS1 had a high immune infiltration score, it exhibited high expression of suppressive immune features. Based on the prediction of immunotherapy and drug sensitivity, we inferred that CS1 may respond poorly to immunotherapy and be less sensitive to targeted drugs. The analysis of bulk data integrated with single-cell data further reflected the high expression of inhibitory immune features in CS1 and the high proportion of malignant tumor cells. And CS2 contained a large number of plasmacytoid B cells, presenting an activated immune microenvironment. Finally, the robustness of our subtypes was successfully validated in four external datasets. Conclusion: In summary, we conducted a comprehensive analysis of multi-omics data with 10 clustering algorithms to reveal the molecular characteristics of KIRC patients and validated the relevant conclusions by single-cell analysis and external data. Our findings discovered new KIRC subtypes and may further guide personalized and precision treatments., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Leptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD., Methods: Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20 mg once every 2 weeks (n = 5) or pembrolizumab 20 mg once every 3 weeks (n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2-9). Efficacy and safety analyses were performed on all treated patients., Results: From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1-45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1)., Conclusions: In this real-world study, intrathecal anti-PD-1 treatment demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fleet electrification is considered to be an important measure for reducing carbon emissions in the road transport industry. Considering the heterogeneity of the NEV market penetration and the vehicle types in different provinces, how to design targeted and time-sequenced road transport decarbonisation reduction strategies has become a key issue that needs to be discussed urgently. In this study, the NEVs ownership in China's 31 provinces is used as an intermediate variable. Considering the process of energy transition and changes in vehicle structure, a two-layer scenario framework that combines Shared Socioeconomic Pathways scenarios and model structure was developed to predict carbon emissions. This study firstly analyzes the electrification process and carbon emission reduction potential of provincial road transport industry by region, vehicle type and stage. The potential for reducing carbon emissions was determined under benchmark, transition, and electrification scenarios. The results indicate that the Pearson Correlation Coefficient-Discrete Wavelet Transform-Bidirectional Long Short-term Memory prediction model has an mean absolute percentage error of 8.583 and an R-squared of 0.975. China's road transportation industry total carbon emissions will reach its peak as early as 2027, due to the rapid implementation of renewable energy and fleet electrification. Shanghai, Jiangsu, Shandong, Henan, and Guangdong have set carbon peak targets that can be achieved faster with the transition plan for new energy vehicles to replace fossil fuel vehicles. This paper proposes a timing-responsive deep decarbonization path and policy recommendations for China's road transport industry in sub provincial and time-series settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

T-cell engagers (TCEs) represent a promising therapeutic strategy for various cancers and autoimmune disorders. These bispecific antibodies act as bridges, connecting T-cell receptors (TCRs) to target cells (either malignant or autoreactive) via interactions with specific tumour-associated antigens (TAAs) or autoantigens to form trimeric synapses, or trimers, that co-localise T-cells with target cells and stimulate their cytotoxic function. Bispecific TCEs are expected to exhibit a bell-shaped dose-response curve, with a defined optimal TCE exposure for maximizing trimer formation. The shape of the dose-response is determined by a non-trivial interplay of binding affinities, exposure and antigens expression levels. Furthermore, excessively low binding to the TCR may reduce efficacy, but mitigate risk of over-stimulating cytokine secretion or induce effector cell exhaustion. These inevitable trade-off highlights the importance of quantitatively understanding the relationship between TCE concentration, target expression, binding affinities, and trimer formation. We utilized a mechanistic target engagement model to show that, if the TCE design parameters are close to the recommended ranges found in the literature, relative affinities for TCR, TAA and target expression levels have qualitatively different, but predictable, effects on the resulting dose-response curve: higher expression levels shift the curve upwards, higher antigen affinity shifts the curve to the left, and higher TCR affinity shifts the curve upwards and to the left., Competing Interests: All authors are employees and shareholders of AstraZeneca Plc., (Copyright © 2024 Lai, Pichardo-Almarza, Verma, Shahinuzzaman, Zhu and Kimko.)

Background: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD)., Aim: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD., Methods: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD., Results: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074)., Conclusions: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD., Competing Interests: Competing interests: TC-FY reported serving as an advisory committee member and a speaker for Gilead Sciences outside the submitted work. EAT reported receiving personal fees as advisory board member for Boehringer, Novo Nordisk, Pfizer and Siemens; receiving speaker fees from Echosens, Novo Nordisk and AbbVie outside the submitted work. HH reported personal fees from AstraZeneca, personal fees from Bristol Myers-Squibb, personal fees from MSD, personal fees from Novo Nordisk, personal fees from Boehringer Ingelheim, personal fees from KOWA and personal fees from GW Phara outside the submitted work, and grants from AstraZeneca, grants from Echosens, grants from Gilead Sciences, grants from Intercept, grants from MSD, grants from Novo Nordisk and grants from Pfizer outside the submitted work. JB reported receiving grants and personal fees from Echosens outside the submitted work. JLC reported receiving other from Echosens Clinical Trials during the conduct of the study; grants from Roche Pharma and other from Gilead Advisory Board outside the submitted work. WKC reported serving as consultant or advisory board member for Zuellig Pharma, Abbott, Roche, AbbVie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Novo Nordisk, Abbott, Echosens, Viatris and Hisky Medical. AJS reported receiving grants from Intercept, personal consulting fees from Gilead, grants from Merck, personal consulting fees from Pfizer, grants and personal consulting fees from Eli Lilly, grants and personal consulting fees from Novo Nordisk, Boehringer Ingelheim, Novartis, Histoindex, and stock options from Genfit, Tiziana, Durect, Inversago and personal consulting fees from Genentech, ALnylam, Regeneron, Zydus, LG chem, Hanmi, Madrigal, Path AI, 89 Bio and stock options from Galmed outside the submitted work. VdL reported receiving non-financial support from Echosens during the conduct of the study. PNN reported receiving grants from Novo Nordisk, advisory board and personal consulting fees, honoraria for lectures and travel expenses from Novo Nordisk, personal consulting and advisory board fees from Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol-Myers Squibb, Pfizer, MSD, Sun Pharma, Eli Lilly, Madrigal, GSK and non-financial support for educational events from AiCME outside the submitted work. LC reported receiving personal fees for consulting and speakers bureau from Echosens during the conduct of the study; personal consultancy fees from Boston pharmaceutical and Gilead, speaker bureau and consultancy personal fees from GSK, personal speaker bureau fees from Inventiva, personal consultancy fees from Madrigal, personal Consultancy fees from MSD and Novo Nordisk, personal consultancy fees from Pfizer, Sagimet and Siemens Healthineers outside the submitted work. CF reported being in the full-time employment of Echosens during the conduct of the study. GL-HW reported receiving personal fees from Echosens during the conduct of the study; grants from Gilead Sciences Research outside the submitted work. MS-WC reported being in the full-time employment of Echosens during the conduct of the study. MR-G reported receiving personal fees from Echosens outside the submitted work. SUK reported personal fees from Gilead Sciences, personal fees from GSK, personal fees from Bayer, personal fees from Eisai, personal fees from AbbVie, personal fees from Echosens, personal fees from MSD, personal fees from Bristol-Myers Squibb and personal fees from AstraZeneca outside the submitted work, and grants from AbbVie, grants from Bristol-Myers Squibb, and grants from Gilead Sciences outside the submitted work. VW-SW reported receiving personal speaker fees from Abbott, consultant and speaker fees from AbbVie, personal consultant fees from Boehringer Ingelheim, Echosens, Gilead Sciences, grants from Gilead Sciences, personal consultant fees from Intercept, Inventiva, Novo Nordisk, personal consultant fees from Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, personal speaker fees from Unilab, personal consultant fees from Visirna, and being a cofounder of Illuminatio outside the submitted work. CDB has received grant support from Echosens. No other disclosures were reported., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Large-scale visual-language pre-trained models (VLPMs) have demonstrated exceptional performance in downstream object detection through text prompts for natural scenes. However, their application to zero-shot nuclei detection on histopathology images remains relatively unexplored, mainly due to the significant gap between the characteristics of medical images and the weboriginated text-image pairs used for pre-training. This paper aims to investigate the potential of the object-level VLPM, Grounded Language-Image Pre-training (GLIP), for zero-shot nuclei detection. Specifically, we propose an innovative auto-prompting pipeline, named AttriPrompter, comprising attribute generation, attribute augmentation, and relevance sorting, to avoid subjective manual prompt design. AttriPrompter utilizes VLPMs' text-to-image alignment to create semantically rich text prompts, which are then fed into GLIP for initial zero-shot nuclei detection. Additionally, we propose a self-trained knowledge distillation framework, where GLIP serves as the teacher with its initial predictions used as pseudo labels, to address the challenges posed by high nuclei density, including missed detections, false positives, and overlapping instances. Our method exhibits remarkable performance in label-free nuclei detection, out-performing all existing unsupervised methods and demonstrating excellent generality. Notably, this work highlights the astonishing potential of VLPMs pre-trained on natural image-text pairs for downstream tasks in the medical field as well. Code will be released at github.com/AttriPrompter.

The electrochemical performances of Ti 3 C 2 T x MXene are severely restricted by the easy oxidation and restacking. Herein, tannic acid (TA) is introduced into Ti 3 C 2 T x dispersion, and the mixed dispersion is further subjected to a simple hydrothermal treatment to prepare the hydrothermal Ti 3 C 2 T x and TA composite (h-Ti 3 C 2 T x @h-TA). Due to the decomposition of TA into gallic acid (GA), hydrothermal TA (h-TA) is a mixture of TA and GA. The strong interaction between h-TA and MXene mainly involves chemical interaction between the hydroxyl groups in h-TA and the surface/edge Ti atoms, along with numerous hydrogen bonds. The h-TA intercalation weakens MXene restacking and increases interlayer spacing, thereby improving ion transport pathways and accessibility. The chemical interaction between the hydroxyl groups of GA and the Ti atoms significantly enhances oxidation resistance and pseudocapacitive active sites. Therefore, the h-Ti 3 C 2 T x @h-TA film electrode shows significantly enhanced capacitance (848 F·g -1 at 1 A g -1 ) and cycling stability (100% retention after 20 000 cycles). Moreover, flexible sandwiched supercapacitors with symmetrical h-Ti 3 C 2 T x @h-TA electrodes exhibit a high energy density of 30.1 Wh kg -1 at a high power density of 300 W kg -1 , outperforming those of Ti 3 C 2 T x -based film electrodes and sandwiched supercapacitors reported so far. The extrusion-printed microsupercapacitors with h-Ti 3 C 2 T x @h-TA electrodes demonstrate high areal capacitance (135 mF cm -2 at 5 mV s -1 ) along with energy storage performance (6.74 μWh cm -2 at 506 μW cm -2 ) and cycling stability (98.8% retention after 41 460 cycles), all while maintaining excellent flexibility. These impressive results indicate the great application potential of the hydrothermal Ti 3 C 2 T x MXene and tannic acid composite in flexible energy storage devices.

Porcine reproductive and respiratory syndrome viruses (PRRSVs) exhibit high mutability and recombination, posing challenges to their immunization and control. This study isolated two new PRRSV strains, GD-7 and GX-3, from samples collected in Guangdong and Guangxi in 2023. Whole-genome sequencing, along with phylogenetic and recombination analyses, confirmed that GD-7 and GX-3 are natural novel recombinant strains of NADC30 PRRSV. Moreover, we established a pathogenicity model for piglets and sows based on the two isolates. The results of piglet pathogenicity revealed that both GD-7 and GX-3 caused clinical symptoms such as fever, loss of appetite, depression, and slow weight gain. Moreover, we observed that the mortality rate of GD-7-inoculated group piglets was 33.3%, which was similar to that of piglets infected with other highly pathogenic PRRSV strains and exceeded the mortality rate of most NADC30-like PRRSV. In pregnant sow models, the survival rate of sows in the GD-7 group was 75%, in contrast to the GX-3 group, where no sow mortality was observed, and both strains resulted in abortion, mummified fetuses, and stillbirths. These results highlight the elevated pathogenicity of these recombinant strains in sows, with GD-7 mainly causing sows to abort, and GX-3 mainly causing sows to give birth to mummified fetuses. This study introduces two distinct clinical recombinant PRRSV strains that differ from the prevalent strains in China. This research furthers our understanding of the epidemiology of PRRSV and underscores the significance of ongoing monitoring and research in the face of evolving virus strains. Moreover, these discoveries act as early warnings, underscoring the necessity for active control and immunization against PRRSV.IMPORTANCESince the discovery of NADC30-like PRRSV in China in 2013, it has gradually become the dominant strain of PRRSV in China. NADC30-like PRRSV exhibits high recombination characteristics, constantly recombining with different strains, leading to the emergence of numerous novel strains. Of particular importance is the observation that NADC30-like PRRSV with different recombination patterns exhibits varying pathogenicity, which has a significant impact on the pig farming industry. This emphasizes the necessity of monitoring and responding to evolving PRRSV strains to develop effective immunization and control strategies. In this paper, we conducted pathogenicity studies on the isolated NADC30-like PRRSV and analyzed the differences in the genomes and pathogenicity of the different strains by recording clinical symptoms, temperature changes, detoxification tests, and changes in viremia and histopathology in infected pigs. This was done to provide a theoretical basis for the epidemiological situation and epidemic prevention and control of PRRSV., Competing Interests: The authors declare no conflict of interest.

Smooth cordgrass ( Spartina alterniflora ) is a native salt marsh plant along the Atlantic coast but has become an invasive species in coastal regions in China, as well as other areas. Utilizing it for resources has become a control measure in reducing the spread of S. alterniflora . This study assesses the nutritional and phytochemical properties of the edible stems of S. alterniflora collected from three locations in Fujian province, China. The tender stems of S. alterniflora exhibit a rich nutritional profile, with high levels of protein, carbohydrates, and fats, and significant amounts of essential vitamins, minerals, and antioxidants, indicating their potential as a nutritious addition to the diet or forage. In addition, the levels of potential contaminants, including nitrate, nitrite, cadmium, lead, and chromium, are below the established safe thresholds for consumption. Our results provide valuable information for the sustainable utilization of S. alterniflora resources and will contribute to the integrated control of S. alterniflora.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs)., Methods: We analyzed data from 3004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and 9 international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs., Results: In the pooled global cohort, the acMASH index identified MASH with an area under the receiver operating characteristic curve (AUROC) of 0.802 (95% confidence interval [CI], 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI, 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI, 0.693-0.800; P < .01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted hazard ratio, 11.23; 95% CI, 3.98-31.66)., Conclusions: This multi-ethnic study validates the acMASH index as a reliable, noninvasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Higher magnesium intake was linked to a lower risk of hepatocellular carcinoma (HCC). However, the relationship between blood magnesium level and HCC has not been fully characterized, especially among patients with liver cirrhosis who are at a higher risk for HCC., Methods: In the Mass General Brigham Biobank, we developed a new prospective cohort of 1,430 patients with liver cirrhosis without liver cancer history using the validated International Classification of Diseases codes. We used Cox proportional hazards models to generate hazard ratios (HRs) with 95% confidence intervals (CI) for incident HCC and used generalized estimating equations to compare changes in liver biomarkers according to baseline blood magnesium, adjusting for age, sex, race, lifestyles, body mass index, type 2 diabetes, model for end-stage liver disease score, and hepatitis infection., Results: During a median follow-up period of 4.26 years, 109 patients developed HCC. Magnesium deficiency (<1.70 mg/dL; N = 158) was associated with a higher risk of HCC (HR = 1.93; 95% CI, 1.12-3.30) compared with magnesium sufficiency (≥1.70 mg/dL; N = 1282). This association remained robust in the 1-year lag analysis (HR = 2.18; 95% CI, 1.11-4.28) and in sensitivity analysis excluding patients with alcoholic liver disease (HR = 2.41; 95% CI, 1.23-4.74). Magnesium in the lowest quartile was associated with a faster increase in alanine transaminase (β = 4.35; 95% CI, 1.06-7.63), aspartate aminotransferase (β = 6.46; 95% CI, 0.28-12.6), direct bilirubin (β = 0.18; 95% CI, 0.01-0.35), and total bilirubin (β = 0.21; 95% CI, 0.03-0.39), compared with the highest quartile., Conclusions: Lower blood magnesium level is associated with higher HCC risk and unfavorable liver biomarker changes., Impact: If confirmed, our findings may potentially enable better identification of high-risk patients for HCC and inform better management strategies for liver cirrhosis., (©2024 American Association for Cancer Research.)

Background: The optimal management of cutaneous melanoma is based on implementing a multidisciplinary tumour board. No studies report cutaneous melanoma patients' perspective along the whole care pathway, taking us through their care experience longitudinally., Aims: To explore the patients' perspective on the cutaneous melanoma care journey in a skin cancers' tertiary referral centre., Methods: A longitudinal qualitative study was designed, using semi-structured interviews. Cutaneous melanoma patients were interviewed three times (T0, after diagnosis; T1, after the first postoperative visit; and T2, at the follow-up). Data were analysed using the inductive framework method., Results: Fifteen patients agreed to participate, and 8 completed all three interviews. We generated three themes describing how patients experienced the care pathway: (i) the evolving need for support during the care pathway, (ii) the development of emotions and expectations for the journey's end, (iii) the changing perceptions of hospital services, the care pathway itself, and the Skin Cancer Unit. We have emphasised the shifts in the experience of receiving assistance from the diagnosis to the follow-up stage. The more the care process progressed, the stronger the need for a relationship with healthcare professionals. The emotional impact of becoming a cancer survivor exacerbated the experience and reflected on patients' perceptions of the care pathway., Conclusions: Adopting a relational approach to reassuring melanoma patients is essential. Our participants expressed needing a medical reference figure as a favourable element. When this is unfeasible, inter-professional training is desirable to help professionals cooperate in a multidisciplinary group and make this collaboration visible to patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Liver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-wide CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell-cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer. Significance: A CRISPR screen reveals AFDN loss as a mediator of liver tropism in colorectal cancer metastasis by decreasing tight junctions in the primary tumor and increasing interactions between cancer cells and hepatocytes., (©2024 American Association for Cancer Research.)

Microglial activation-mediated neuroinflammation is a major contributor to neuronal damage after cerebral ischemia. The Fractalkine (FKN)/CX3C chemokine receptor 1 (CX3CR1) axis plays a critical role in regulating microglial activation and neuroinflammation. The aim of this study is to ascertain the role and mechanism of FKN/CX3CR1 axis in hypoxic postconditioning (HPC)-induced anti-inflammatory and neuroprotective effects on transient global cerebral ischemia (tGCI). We found that HPC suppressed microglial activation and alleviated neuroinflammation in hippocampal CA1 after tGCI. Meanwhile, HPC upregulated the expression of FKN and CX3CR1 in neurons, but it downregulated the expression of CX3CR1 in glial cells after tGCI. In addition, the overexpression of FKN induced by the administration of FKN-carried lentivirus reduced microglial activation and inhibited neuroinflammation in CA1 after tGCI. Furthermore, silencing CX3CR1 with CX3CRi-carried lentivirus in CA1 after tGCI suppressed microglial activation and neuroinflammation and exerted neuroprotective effects. Finally, the overexpression of FKN caused a marked increase of neuronal CX3CR1 receptors, upregulated the phosphorylation of Akt, and reduced neuronal loss of rats in CA1 after tGCI. These findings demonstrated that HPC protected against neuronal damage in CA1 of tGCI rats through inhibiting microglial activation and activating Akt signaling pathway via FKN/CX3CR1 axis., (© 2024. The Author(s).)

With the development of new technologies in recent years, researchers have made significant progress in crop breeding. Modern breeding differs from traditional breeding because of great changes in technical means and breeding concepts. Whereas traditional breeding initially focused on high yields, modern breeding focuses on breeding orientations based on different crops' audiences or by-products. The process of modern breeding starts from the creation of material populations, which can be constructed by natural mutagenesis, chemical mutagenesis, physical mutagenesis transfer DNA (T-DNA), Tos17 (endogenous retrotransposon), etc. Then, gene function can be mined through QTL mapping, Bulked-segregant analysis (BSA), Genome-wide association studies (GWASs), RNA interference (RNAi), and gene editing. Then, at the transcriptional, post-transcriptional, and translational levels, the functions of genes are described in terms of post-translational aspects. This article mainly discusses the application of the above modern scientific and technological methods of breeding and the advantages and limitations of crop breeding and diversity. In particular, the development of gene editing technology has contributed to modern breeding research.

Objective: To investigate the expression of inositol polyphosphate 4-phosphatase type Ⅱ B (INPP4B) in colorectal cancer (CRC) and the relevant clinical significance, to determine the relationship between INPP4B and matrix metallopeptidase 7 (MMP7) in CRC cells, and to make preliminary exploration of the effects of INPP4B on the proliferation and migration of CRC cells and mechanisms involved., Methods: The TIMER2.0 and GEPIA2 databases were used to analyze the differences in INPP4B expression between cancer and para-cancerous tissues and the effects of such differences on the prognosis of CRC. The expression of INPP4B in 102 surgically resected CRC tumors was determined by immunohistochemistry (IHC), and the correlation between INPP4B and clinical pathological indicators was analyzed. In CRC cells with overexpressed/knocked-down INPP4B , the expression of INPP4B and MMP7 were examined by real time fluorogenic quantitative PCR, the protein expression of INPP4B was assessed by Western blot, cell proliferation was determined using the CellTiter 96® AQueous One assay, and cell migration and invasion were assessed using wound healing assay and real-time label-free dynamic cell analysis (RTCA). The LinkedOmics database was used to analyze signaling pathways related to INPP4B function, and the role of potential key molecules was validated at the cellular level., Results: Analysis with the TIMER2.0 database and GEPIA2 database showed elevated INPP4B expression (colon adenocarcinoma [COAD]: 2.30, rectal adenocarcinoma [READ]: 2.33) in CRC compared to normal tissue (COAD: 1.91, READ: 1.89). IHC testing confirmed that INPP4B was upregulated in clinical CRC tissues and paracancerous tissues ( P <0.001). Cox regression model analysis showed that INPP4B (hazards ratio [HR]=1.457, 95% confidence interval [CI]: 1.003-2.115) affected the prognosis of CRC, and the Kaplan-Meier curve showed that patients with high INPP4B expression had shorter overall survival ( P <0.05). χ 2 test was performed to analyze the relationship between INPP4B expression and clinicopathological indexes, and it was found that high expression of INPP4B was correlated with lymph node metastasis ( χ 2 =3.997, P =0.046) and neural invasion( χ 2 =8.511, P =0.004). In in vitro experiments, CRC cells overexpressing INPP4B showed a significantly increased cell proliferation and migration compared to the cells in the control group ( P <0.05). Analysis using the LinkedOmics database showed that INPP4B was correlated with extracellular matrix remodeling and cell migration. Pearson's correlation analysis showed that MMP7 was positively correlated with INPP4B ( r =0.3782, P <0.001). INPP4B overexpression or knockdown in vitro also led to the upregulation or the downregulation of MMP7 expression in CRC cells., Conclusion: INPP4B is highly expressed in CRC tissues and significantly correlated with lymph node metastasis, neural invasion, and patient prognosis. MMP7 may mediate the role of INPP4B in promoting CRC cell migration and invasion., Competing Interests: 利益冲突　本文作者王玉芳是本刊编委会编委。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objectives: To investigate the role of Morinda officinalis polysaccharide (MOP) in the protein expression of the Wnt/β-catenin signaling cascade during the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and to elucidate the mechanisms by which MOP enhances osteogenic differentiation at the cellular level., Methods: BMSCs were isolated and cultured using the whole bone marrow adherence method, followed by flow cytometry for the detection of BMSC marker antigens. Two groups were prepared: a low-dose MOP (L-MOP, 10 µg/mL) group and a high-dose MOP (H-MOP, 40 µg/mL) group. MTT assays and cell clone formation assays were performed to evaluate the effects of different MOP doses on BMSC proliferation. Alizarin red staining (ARS) and alkaline phosphatase (ALP) staining were conducted to assess the impact of varying MOP doses on nodule calcification and ALP activity in BMSCs. Additionally, western blot assays were carried out to determine the effects of different MOP concentrations on the expression levels of osteogenesis-related factors and Wnt/β-catenin pathway proteins in BMSCs., Results: Highly purified BMSCs were successfully extracted. Subsequent assays demonstrated that BMSCs exhibited enhanced proliferation at all MOP doses, particularly at the H-MOP dose, compared to the control group. Both L-MOP and H-MOP increased calcium content and ALP activity in BMSCs, as well as elevated the expression of osteogenic factors and Wnt/β-catenin pathway proteins compared to the blank control group. However, the addition of Dickkopf-1 (DKK1) significantly reduced BMSC proliferation and osteogenic differentiation compared to the H-MOP group., Conclusions: MOP can enhance BMSC proliferation and osteogenic differentiation by activating the Wnt/β-catenin signaling pathway., Competing Interests: None., (AJTR Copyright © 2024.)

The Veterans Health Administration (VHA) listed the infliximab (IFX) biosimilar, IFX-dyyb (Inflectra), on the Veterans Affairs National Formulary (VANF) in May 2017. In September 2018, biosimilar IFX-abda (Renflexis) became the VANF IFX product. The recommended formulary changes from one IFX biosimilar to another provided a unique opportunity to study IFX utilization patterns in IFX-naïve Veterans with Inflammatory Bowel Disease (IBD). This study aimed to describe IFX and healthcare utilization during the 365 days after initiation with IFX reference product (RP) or biosimilars IFX-dyyb and IFX-adba. This descriptive study was performed using the VHA Corporate Data Warehouse. All Veterans initiated on IFX-RP (Remicade) or biosimilars IFX-dyyb and IFX-adba between September 1, 2016 and December 30, 2019 were included and followed for 365 days. Veterans enrolled in the VHA for at least 365 days with no evidence of IFX before their index date were considered IFX-naïve. Continuous data on IFX use, laboratory measurements, and healthcare utilization were reported with means, 95% confidence interval (CI), medians, and interquartile ranges. Frequency, proportions, and 95% CIs were presented for categorical variables. Statistical tests included ANOVA and Kruskal-Wallis for continuous outcomes, Poisson regression for count-based outcomes (i.e., healthcare utilization visits), and Chi-square for dichotomous outcomes. The study identified 1763 IFX-naïve patients with IBD, and 785, 441, and 537 was indexed to RP, IFX-dyyb, and IFX-adba, respectively. Statistical differences were observed in IFX utilization measures related to dosing, adherence, and persistence. The proportion of days covered (PDC) during the 365-day follow-up period varied among the IFX groups: IFX-RP at 66%, IFX-dyyb at 60%, and IFX-abda at 69% (P value < .001). Persistence with the index IFX product during the 365-day follow-up period also varied: IFX-RP at 43%, IFX-dyyb at 32%, and IFX-abda at 51% (P value < .001). Healthcare utilization and laboratory findings were similar among the IFX groups. IFX utilization and laboratory patterns were clinically similar among the IFX biosimilars and RP groups, suggesting that providers did not modify their practice with biosimilars. Statistically significant differences in IFX utilization patterns are explained by formulary dynamics when the VANF product switched from IFX-dyyb to IFX-abda., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Steatotic liver disease (SLD) and chronic kidney disease (CKD) are common conditions that are strongly associated. Yet, there is a paucity of data regarding the prevalence of this overlap and the factors that may drive its occurrence., Methods: Using the National Health and Nutrition Examination survey, we examined trends among adult participants from 2005 - 2020 that defined SLD with the Fatty Liver Index. We completed correlative analyses among adult participants from 2017 - 2020 that defined SLD based on FibroScan results. We utilized multivariable survey-weighted binomial generalized linear models to determine the factors that were associated with CKD, defined as eGFR <60 or urine albumin-creatinine-ratio >30., Results: Among the 76,496 participants included in the trend analyses, the estimated prevalence of CKD was 15.7% (95%CI 15.2 - 16.2%) and SLD was 42.3% (95%CI 41.4 - 43.2%). As compared to those without SLD, those with SLD had a significantly higher estimated prevalence of CKD (SLD: 15.7%, 95%CI 14.9 - 16.5% v. No SLD 11.2%, 95%CI 10.7 - 11.7%). In multivariate analyses of 3,667 participants who underwent FibroScan and had SLD by Fatty Liver Index, adjusting for control and presence of DM, HTN, and HLD, compared to those with normal liver stiffness, those with moderate scarring (F2) had similar odds of CKD (1.53, 95CI 0.91-2.56), those with severe scarring (F3) had higher odds of CKD (2.28, 95CI 1.20-4.32), and those with cirrhosis had higher odds of CKD (2.21, 95CI 1.13-4.32)., Conclusions: Our findings highlight that CKD is common among patients with SLD and that higher degrees of hepatic fibrosis are associated with CKD, independent of other co-morbidities of the metabolic syndrome., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background: Sanfeng Tongqiao Dripping Pills (SFTQ) has clinically demonstrated a promising therapeutic effect on allergic rhinitis (AR). However, the active ingredients and underlying mechanisms of SFTQ remain unclear., Purpose: Exploring the effects, mechanisms, and active ingredients of SFTQ in the treatment of AR is valuable., Study Design: The mechanisms of SFTQ and its active ingredients in treating AR were investigated through in vivo and in vitro studies., Methods: A HDM-induced AR model was established in BALB/c mice. The effects of SFTQ in treating AR were evaluated by AR-like symptoms, EOS count, and pathological changes in the nasal tissue in vivo. The effects of SFTQ active components on epithelial cells (ECs) were evaluated in Poly(I:C) and TNF-α co-stimulated human nasal ECs (RPMI-2650). Additionally, the effects of SFTQ active components on splenocytes proliferation and Th cell differentiation were assessed. A co-culture system of ECs and T lymphocytes was established to investigate the impact of Th2 cells on the structure and function of ECs. The effects of SFTQ ingredients on ECs, T lymphocytes, and the HDM-induced AR model were further confirmed through in vivo and in vivo studies, respectively., Results: SFTQ significantly alleviated AR-like symptoms and pathological changes in the nasal tissue of AR mice. The treatment elevated the expression of Occludin and E-cadherin in the nasal epithelium and reduced the percentage of Th2 cells in cervical lymph nodes (CLN). Among the active compounds of SFTQ, L-Menthone and Pulegone notably downregulated IL-33 levels in activated ECs, while Hesperetin significantly decreased TSLP and IL-33 levels. In the co-culture system of ECs and Th2 cells, exposure to Baicalin, Wogonin, and Pulegone increased the TEER value of ECs, while notably inhibiting the production of TSLP and IL-33. Furthermore, in HDM-induced AR mice, treatments with Baicalin, Luteolin, and Hesperetin effectively inhibited AR-like symptoms. Additionally, Luteolin and Hesperetin significantly reduced the inflammatory cells infiltration and the population of Th2 cells in AR mice., Conclusion: SFTQ and its active ingredients effectively alleviated HDM-induced AR in mice by inhibiting Th2 cell differentiation and repairing the nasal epithelial barrier. Our study can provide a scientific basis for SFTQ to be used in clinical treatment of AR., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Minyi Lai, Shuxian Sun, Tongwen Zuo, Lin Li, Jie Zheng, Min Hong reports equipment, drugs, or supplies was provided by Yangtze River Pharmaceutical Group. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Since the pathogenesis of depression is complex, antidepressant therapy remains unsatisfactory. Recent evidence suggests a link between depression and lipid metabolism. Saikosaponin (SS) exhibits antidepression and lipid-regulating effects in modern pharmacology. However, it is unknown whether lipid regulation is the key mechanism of the SS antidepressant effect and how it works., Purpose: In this study, we investigated the relationship between the antidepressant activity of SS and the regulation of lipid metabolism and explored potential mechanisms., Methods: APOE -/- mice, in combination with the chronic unpredictable mild stress (CUMS) model, were used to study the relationship between SS antidepressant activity and lipid metabolism through behavioral, electrophysiological techniques, and non-targeted lipidomics. Western blot, primary cell culture technology, and laser speckle cerebral blood flow imaging were employed to elucidate potential mechanisms. GraphPad Prism was used for statistical analysis, and p < 0.05 was considered statistically significant., Results: APOE -/- mice exhibit more severe depressive-like behavior and dysregulation of sphingolipid metabolism in CUMS. SS alleviates depressive behavior and cortical sphingolipid metabolism disorder caused by CUMS, but has no effect on APOE -/- mice. SS alleviates the imbalance between ceramide (Cer) and sphingomyelin (SM) through acidic sphingomyelinase (AMSase). In addition, SS regulates neuronal glutamate release via sphingolipid metabolism, thereby alleviating the CUMS-induced inhibition of neurovascular coupling (regulates metabotropic glutamate receptor and IP3 receptor), which ameliorates the reduction of cerebral blood flow in depressed mice., Conclusion: Our study highlights the role of lipid metabolism in the antidepressant activity of SS and explores its underlying mechanisms. This study provided new insights into the better understanding of the antidepressant mechanisms of phytomedicine while increasing the possibility of lipid metabolism as a therapeutic strategy for depression., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aim: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM)., Materials and Methods: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis., Results: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05)., Conclusion: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM., (© 2024 John Wiley & Sons Ltd.)

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

Rationale: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear., Objectives: This study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD., Methods: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting., Results: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats., Conclusions: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD., (© 2024. The Author(s).)

Hydrogen sulfide (H 2 S) has emerged as a crucial signaling molecule in plant stress responses, playing a significant role in regulating various physiological and biochemical processes. In this study, we report an aggregation-induced emission (AIE)-based ratiometric fluorescent probe TPN-H 2 S for the highly selective detection of H 2 S in plant tissues. The probe exhibited excellent sensitivity and selectivity towards H 2 S over other analytes, enabling real-time monitoring of H 2 S dynamics in living cell. Furthermore, the AIE-based ratiometric probe TPN-H 2 S allowed for accurate quantification of H 2 S levels, providing valuable insights into the spatiotemporal distribution of Cys metabolism produces H 2 S. Importantly, the physiological pathways and signaling mechanisms of H 2 S production of was investigated in plant tissues under Cr and nano-plastics stress. Utilizing a high-throughput screening approach, we identified exogenous substances such as calcium chloride (CaCl 2 ) and abscisic acid (ABA) that could induce higher level of H 2 S production during the stress response in plants. Overall, those findings demonstrate the potential of the AIE-based ratiometric fluorescent probe TPN-H 2 S as a powerful tool for unraveling the role of H 2 S in plant stress responses and pave the way for further exploration of H 2 S-mediated signaling pathways in plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In traditional Chinese medicinal practices, Gegen (GG) and Tianma (TM) are widely utilized for headache relief, but their material basis has not been comprehensively characterized. This research utilized ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) for precise determination of Gegen-Tianma's (GGTM) material composition, and employed desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to pinpoint the brain-absorbed components and various metabolites post oral administration to rats. A total of 80 chemical constituents were identified from GGTM, 11 prototypes and 18 metabolites were identified from plasma. The brain tissue was identified in total 4 prototypes and 5 metabolites, these constituents were basically located in the prefrontal cortex and thalamus. The absorption patterns of components in the rat brain aligned with the varied distribution of metabolites within the brain. This study provides a solid theoretical basis for in-depth exploration of potential drug targets and elucidation of the specific mechanism of action of GGTM in the treatment of migraine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG., Methods: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis., Results: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SR dif ), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively., Conclusion: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response., Clinical Relevance Statement: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG., Key Points: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is Linbo Cai. Conflict of Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and Biometry No complex statistical methods were necessary for this paper. Informed consent Written informed consent was waived by the Institutional Review Board. Ethical approval Institutional Review Board approval was obtained (approval number: 2022-010-020). Study subjects or cohorts overlap Some study subjects or cohorts have been previously reported in “The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.” The previous study topic was prognostic factors related to DIPG. However, the current study focuses on predicting DIPG radiotherapy response, which is a completely different research topic compared to the previously published work. Methodology RetrospectiveCross-sectional studyPerformed at one institution, (© 2024. The Author(s).)

Background and Aim: Yueju Pill (YJ) not only has good antidepressant effect but also can effectively treat digestive system diseases. However,it remains unclear whether the mechanism of antidepressant action of YJ is related to the peripheral digestive system. The purpose of this study was to elucidate the antidepressant mechanism of YJ on ghrelin level based on gastric mTOR/S6K signal pathway and sensitized hippocampal Ghrelin/GHS-R system in CUMS mice., Experimental Procedure: The depression model was induced by chronic unpredictable mild stress (CUMS) and social isolation. The antidepressant effect of YJ was observed by behavioral experiment and hemodynamic experiments. Ghrelin levels in in hippocampus and blood were measured by Elisa kit, and the mRNA of ghrelin in mice stomach was measured by Real-time Quantitative PCR (RT-qPCR). The activation level of gastric mTOR/S6K signal pathway was detected by Western Blot (WB). Rapamycin (Rapa) and L-Leucine (L-Leu) were used to verify the effects of YJ on the synthesis and release of ghrelin. The activity of GHS-R in hippocampus was observed by immunofluorescence. Hippocampal neuronal damage was evaluated by HE staining and Nissl staining. The level of central neurotransmitter was measured by liquid chromatograph mass spectrometer (LC-MS)., Results and Conclusion: YJ ameliorates CUMS-induced depressive-like behavior by inhibiting the gastric mTOR/S6K signaling pathway and increasing GHR expression in the mouse stomach. However, these effects of YJ could be resisted by L-Leu (a mTOR receptor agonist). Further studies have shown that YJ can sensitize the Ghrelin/GHS-R system in the hippocampus, with significant neuroprotective effects, and is also involved in regulating the levels of key neurotransmitters (5-hydroxytryptamine, Dopamine and γ-aminobutyric acid) in depressive-like states., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)