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Deep ultraviolet (DUV) nonlinear optical (NLO) crystals with balanced performance are crucial for extending laser wavelengths into the DUV region, essential for various laser applications. However, developing ideal DUV crystals is challenging due to stringent requirements: strong second-harmonic generation (SHG) response, short cut-off wavelength, and effective phase-matching behavior. DUV NLO borates, which feature π-conjugated groups, have garnered attention for their higher SHG coefficients compared to phosphates. However, phosphates typically show short UV cut-off edges due to the large HOMO-LUMO gap (approximately 9.6 eV) of the [PO₄] units. To enhance the SHG effect while maintaining DUV transparency in phosphates, several strategies have been proposed: 1) using distorted polymerized P-O groups like isolated C₁-[P₃O₁₀]⁵⁻ and [P₂O₇]⁴⁻; 2) aligning isolated [PO₄]³⁻ tetrahedra along the polar screw axis; 3) introducing additional NLO-active units; and 4) exploring new units derived from [PO₄]³⁻, such as [PO₃F]²⁻ tetrahedra. These strategies have led to the successful development of various non-centrosymmetric phosphates, highlighting their potential as DUV NLO candidates. This review explores the relationship between their crystal structures and DUV NLO performance, and proposes future directions for developing ideal DUV NLO materials., (© 2024 Wiley‐VCH GmbH.)

Background: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study., Methods: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR)., Results: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003)., Conclusion: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism., Methods: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 μg/mL). AGS cells treated with 200 μg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups ( n  = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded., Results: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects., Conclusion: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.

The efficient detection of the Néel vector in antiferromagnets is one of the prerequisites toward antiferromagnetic spintronic devices and remains a challenging problem. Here, we propose that the layer Hall effect can be used to efficiently detect the Néel vector in centrosymmetric magnetoelectric antiferromagnets. Thanks to the robust surface magnetization of magnetoelectric antiferromagnets, the combination of sizable exchange field and an applied electric field results in the layer-locked spin-polarized band edges. Moreover, the Berry curvature can be engineered efficiently by an electric field, which consequently gives rise to the layer-locked Berry curvature responsible for the layer Hall effect. Importantly, it is demonstrated that the layer Hall conductivity strongly depends on the Néel vector orientation and exhibits rich electromagnetic responses, which can be used to detect the Néel vector reversal. Based on density functional theory calculations, we exemplify those phenomena in the prototypical Cr&#95;{2}O&#95;{3} compound. A complete list of the magnetic point groups sustaining the layer Hall effect is presented, aiding the search for realistic materials. Our work proposes a novel approach to detect the Néel vector and holds great promise for antiferromagnetic spintronic applications.

The longitudinal nonreciprocal charge transport (NCT) in crystalline materials is a highly nontrivial phenomenon, motivating the design of next generation two-terminal rectification devices (e.g., semiconductor diodes beyond PN junctions). The practical application of such devices is built upon crystalline materials whose longitudinal NCT occurs at room temperature and under low magnetic field. However, materials of this type are rather rare and elusive, and theory guiding the discovery of these materials is lacking. Here, we develop such a theory within the framework of semiclassical Boltzmann transport theory. By symmetry analysis, we classify the complete 122 magnetic point groups with respect to the longitudinal NCT phenomenon. The symmetry-adapted Hamiltonian analysis further uncovers a previously overlooked mechanism for this phenomenon. Our theory guides the first-principles prediction of longitudinal NCT in multiferroic ϵ-Fe&#95;{2}O&#95;{3} semiconductor that possibly occurs at room temperature, without the application of external magnetic field. These findings advance our fundamental understandings of longitudinal NCT in crystalline materials, and aid the corresponding materials discoveries.

Background: Acute pancreatitis (AP) is a disease caused by abnormal activation of pancreatic enzymes and can lead to self-digestion of pancreatic tissues and dysfunction of other organs. Enteral nutrition plays a vital role in the treatment of AP because it can meet the nutritional needs of patients, promote the recovery of intestinal function, and maintain the barrier and immune functions of the intestine. However, the risk of aspiration during enteral nutrition is high; once aspiration occurs, it may cause serious complications, such as aspiration pneumonia, and suffocation, posing a threat to the patient's life. This study aims to establish and validate a prediction model for enteral nutrition aspiration during hospitalization in patients with AP., Aim: To establish and validate a predictive model for enteral nutrition aspiration during hospitalization in patients with AP., Methods: A retrospective review was conducted on 200 patients with AP admitted to Chengdu Shangjin Nanfu Hospital, West China Hospital of Sichuan University from January 2020 to February 2024. Clinical data were collected from the electronic medical record system. Patients were randomly divided into a validation group ( n = 40) and a modeling group ( n = 160) in a 1:4 ratio, matched with 200 patients from the same time period. The modeling group was further categorized into an aspiration group ( n = 25) and a non-aspiration group ( n = 175) based on the occurrence of enteral nutrition aspiration during hospitalization. Univariate and multivariate logistic regression analyses were performed to identify factors influencing enteral nutrition aspiration in patients with AP during hospitalization. A prediction model for enteral nutrition aspiration during hospitalization was constructed, and calibration curves were used for validation. Receiver operating characteristic curve analysis was conducted to evaluate the predictive value of the model., Results: There was no statistically significant difference in general data between the validation and modeling groups ( P > 0.05). The comparison of age, gender, body mass index, smoking history, hypertension history, and diabetes history showed no statistically significant difference between the two groups ( P > 0.05). However, patient position, consciousness status, nutritional risk, Acute Physiology and Chronic Health Evaluation (APACHE-II) score, and length of nasogastric tube placement showed statistically significant differences ( P < 0.05) between the two groups. Multivariate logistic regression analysis showed that patient position, consciousness status, nutritional risk, APACHE-II score, and length of nasogastric tube placement were independent factors influencing enteral nutrition aspiration in patients with AP during hospitalization ( P < 0.05). These factors were incorporated into the prediction model, which showed good consistency between the predicted and actual risks, as indicated by calibration curves with slopes close to 1 in the training and validation sets. Receiver operating characteristic analysis revealed an area under the curve (AUC) of 0.926 (95%CI: 0.8889-0.9675) in the training set. The optimal cutoff value is 0.73, with a sensitivity of 88.4 and specificity of 85.2. In the validation set, the AUC of the model for predicting enteral nutrition aspiration in patients with AP patients during hospitalization was 0.902, with a standard error of 0.040 (95%CI: 0.8284-0.9858), and the best cutoff value was 0.73, with a sensitivity of 91.9 and specificity of 81.8., Conclusion: A prediction model for enteral nutrition aspiration during hospitalization in patients with AP was established and demonstrated high predictive value. Further clinical application of the model is warranted., Competing Interests: Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

Background: There is limited knowledge on international trends in topical calcineurin inhibitor (TCI) utilization. Objective: To describe international TCI utilization trends from 2012 to 2019 and evaluate the relationship of country-level economic status, geographic location, and atopic dermatitis (AD) disease burden with drug utilization. Methods: We used IQVIA MIDAS ® pharmaceutical quarterly sales data to attain country-level purchasing of TCIs in grams from 2012 to 2019. A multivariable linear regression estimated the association between countries' sociodemographic index (SDI), AD disability-adjusted life year (DALY) rates, and geographic location with TCI utilization. Results: A total of 68 countries were included in our analysis. From 2012 to 2019, overall TCI utilization increased by 66% but remained 11.2 times higher in high-sociodemographic compared with low-middle/low-sociodemographic countries. SDI and geographic location were associated with greater TCI utilization in multivariable analyses, whereas AD DALY rates were not. High-SDI countries used 21,476 grams (95% confidence interval [CI]: 11,915 to 31,036) and high-middle SDI countries used 9,403 grams (95% CI: -393 to 19,200) more TCIs per 100,000 people compared with low-middle/low-SDI countries, respectively. Northern hemisphere countries used 8,588 grams more TCIs per 100,000 people (95% CI: 612 to 16,564). Conclusions: We demonstrated greater TCI utilization among high-SDI compared with lower SDI countries.

Colorectal cancer (CRC) is one of the most common tumors of the digestive system worldwide. KRAS mutations limit the use of anti-EGFR antibodies in combination with chemotherapy for the treatment of CRC. Therefore, novel targeted therapies are needed to overcome the KRAS-induced oncogenesis. Recent evidence suggests that inhibition of PI3K led to ferroptosis, a nonapoptotic cell death closely related to KRAS-mutant cells. Here, we showed that a selective PI3Kδ inhibitor TYM-3-98 can suppress the AKT/mTOR signaling and activate the ferroptosis pathway in KRAS-mutant CRC cells in a concentration-dependent manner. This was evidenced by the lipid peroxidation, iron accumulation, and depletion of GSH. Moreover, the overexpression of the sterol regulatory element-binding protein 1 (SREBP1), a downstream transcription factor regulating lipid metabolism, conferred CRC cells greater resistance to ferroptosis induced by TYM-3-98. In addition, the effect of TYM-3-98 was confirmed in a xenograft mouse model, which demonstrated significant tumor suppression without obvious hepatoxicity or renal toxicity. Taken together, our work demonstrated that the induction of ferroptosis contributed to the PI3Kδ inhibitor-induced cell death via the suppression of AKT/mTOR/SREBP1-mediated lipogenesis, thus displaying a promising therapeutic effect of TYM-3-98 in CRC treatment., (© 2024. The Author(s).)

Ferroelectricity in CMOS-compatible hafnia (HfO&#95;{2}) is crucial for the fabrication of high-integration nonvolatile memory devices. However, the capture of ferroelectricity in HfO&#95;{2} requires the stabilization of thermodynamically metastable orthorhombic or rhombohedral phases, which entails the introduction of defects (e.g., dopants and vacancies) and pays the price of crystal imperfections, causing unpleasant wake-up and fatigue effects. Here, we report a theoretical strategy on the realization of robust ferroelectricity in HfO&#95;{2}-based ferroelectrics by designing a series of epitaxial (HfO&#95;{2})&#95;{1}/(CeO&#95;{2})&#95;{1} superlattices. The designed ferroelectric superlattices are defects free, and most importantly, on the base of the thermodynamically stable monoclinic phase of HfO&#95;{2}. Consequently, this allows the creation of superior ferroelectric properties with an electric polarization >25  μC/cm^{2} and an ultralow polarization-switching energy barrier at ∼2.5  meV/atom. Our work may open an avenue toward the fabrication of high-performance HfO&#95;{2}-based ferroelectric devices.

Aims: PI3Kδ is expressed predominately in leukocytes and is commonly found to be aberrantly activated in human B-cell lymphomas. Although PI3Kδ has been intensively targeted for discovering anti-lymphoma drugs, the application of currently approved PI3Kδ inhibitors has been limited due to unwanted systemic toxicities, thus warranting the development of novel PI3Kδ inhibitors with new scaffolds., Main Methods: We designed TYM-3-98, an indazole derivative, and evaluated its selectivity for all four PI3K isoforms, as well as its efficacy against various B-cell lymphomas both in vitro and in vivo., Key Findings: We identified TYM-3-98 as a highly selective PI3Kδ inhibitor over other PI3K isoforms at both molecular and cellular levels. It showed superior antiproliferative activity in several B-lymphoma cell lines compared with the approved first-generation PI3Kδ inhibitor idelalisib. TYM-3-98 demonstrated a concentration-dependent PI3K/AKT/mTOR signaling blockage followed by apoptosis induction. In vivo, TYM-3-98 showed good pharmaceutical properties and remarkably reduced tumor growth in a human lymphoma xenograft model and a mouse lymphoma model., Significance: Our findings establish TYM-3-98 as a promising PI3Kδ inhibitor for the treatment of B-cell lymphoma., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Preeclampsia (PE) is a pregnancy-associated hypertension disorder with high morbidity and mortality. Short-chain fatty acids (SCFAs)-molecules produced by gut microbes-have been associated with hypertension, yet their relation to PE remains uncertain., Objectives: The aim was to review existing human studies that examined associations of the major SCFAs (acetate, propionate, butyrate) in pregnancy with PE development., Methods: Two reviewers independently searched online databases (EMBASE, PubMed, Web of Science, and Cochrane Database of Systematic Reviews) in January 2024 using the following terms: "short-chain fatty acids," "acetic acid," "butyric acid," "propionic acid," and "preeclampsia." The final set of included studies had to report associations of SCFAs with PE, be peer-reviewed, be written in English, and be conducted in humans., Results: The abstracts of 907 studies were screened; 43 underwent full-text screening and 11 (1318 total participants, 352 with PE) were included in the final review. All studies used a case-control design. SCFAs were measured in a range of biospecimens (eg, serum, plasma, feces, placentas, and amniotic fluid) that were collected at distinct time points in pregnancy. All 7 studies that investigated butyrate found that it was lower in PE cases than in controls, with 6 of these showing statistical significance (P < .05). Five studies showed that acetate was significantly lower in individuals with PE compared with healthy individuals, while 1 study found that acetate was significantly higher in PE cases. One study reported significantly higher propionate among PE cases vs controls, while 2 studies reported significantly lower propionate levels in PE cases. The nuance in results for acetate and propionate may owe to reasons such as differences in distributions of population characteristics associated with SCFA level and PE or type of PE (early vs late)., Conclusion: Current epidemiologic evidence, which derives only from case-control studies, suggests that SCFAs, particularly butyrate (protective), in pregnancy are related to the development of PE. Large-cohort studies are warranted to investigate the temporality and potential causality of these associations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Cannabis use has been associated with reduced physical activity and increased sedentary behavior in adolescents. In adults, however, there is no conclusive evidence of such an association, and existing studies have primarily relied on self-reported activity measures. As cannabis use increases globally, a deeper understanding of its relationship with activity levels may inform clinical counseling and guidelines. This study investigated the association between recent cannabis use and accelerometer-measured activity. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. We included adults in the United States who responded to a cannabis questionnaire and had at least 4 days of activity data from an ActiGraph GT3X+ accelerometer, which comprised participants from 18 to 59 years. The primary exposure was any self-reported cannabis use in the past 30 days. The primary outcome was daily sedentary time and secondary outcomes were daily light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Analyses were performed with multivariable quasi-Poisson regression models. Results: Of 4666 included adults, 658 (14.1%) reported recent cannabis use. After covariate adjustment, recent cannabis use was not associated with daily sedentary time (adjusted incidence rate ratio [aIRR] 0.99, 95% confidence interval [CI]: 0.98-1.01) or daily MVPA time (aIRR 1.01, 95% CI: 0.98-1.04). Daily LPA time was 4% greater with recent cannabis use (aIRR 1.04, 95% CI: 1.01-1.06). Conclusion: Recent cannabis use in young to midlife adults was not associated with accelerometer-measured sedentary or MVPA time, but it was associated with a marginal increase in LPA time of unclear clinical significance. Our findings provide evidence against existing concerns that cannabis use independently promotes sedentary behavior and decreases physical activity. Future prospective studies are needed to determine if these findings generalize to specific populations using cannabis including chronic pain patients.

Species within Tetraplosphaeriaceae have been frequently documented in recent years with the extensive investigations of microfungi along a latitudinal gradient from north to south in the Asian/Australian region. Both bamboo substrates and freshwater habitats serve as extensive reservoirs, hosting a rich diversity of fungi that exhibit broad geographical distributions. The most common fungi in these two environments are generally distributed in distinct families. However, our statistics have revealed an intriguingly distinct preference of Tetraplosphaeriaceae species for inhabiting both bamboo substrates and freshwater habitats. The genera Pseudotetraploa (100%) and Triplosphaeria (100%) exhibit a strong preference, followed by Shrungabeeja (71%) and Quadricrura (67%). Our taxonomic and phylogenetic study of microfungi in southern China have identified four additional novel species, viz., Aquatisphaeria bambusae sp. nov., Pseudotetraploa phyllostachydis sp. nov., Pseudotetraploa yangjiangensis sp. nov., and Tetraploa submersa sp. nov. from bamboo substrates and freshwater habitats. In addition, Aquatisphaeria thailandica has previously been documented from freshwater habitats in Thailand; however, we have once again isolated this species from decaying bamboo substrates in Guangdong, China. The new findings substantiate our hypothesis that the preference of Tetraplosphaeriaceae species for colonizing bamboo substrates and freshwater habitats will be more evident through more extensive investigations conducted in such environments.

Background: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described., Objectives: To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization., Methods: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization., Results: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60)., Limitations: Missing medication utilization data for some countries., Conclusion: High-income countries use more topical AK therapies than middle-income countries., Competing Interests: MT received consulting fees from CADTH and Health Canada. NJL is a trustee of the British Association of Dermatologists. AMD has received compensation from the British Journal of Dermatology (reviewer and Section Editor), American Academy of Dermatology (guidelines writer), National Eczema Association (grant reviewer), Canadian Dermatology Today (manuscript writer) and Canadian Agency for Drugs and Technologies in Health (consultant). AMD has received research grants to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, US National Institutes of Health and Physicians Services Incorporated Foundation., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Introduction: Perineal hernia (PH) is a rare complication that can occur after abdominoperineal resection for rectal cancer. Laparoscopic repair of PHs has gained increasing popularity compared to open approaches due to advantages such as superior visualization, decreased invasiveness, and faster recovery. This case report highlights the successful use of laparoscopic tension-free mesh repair for concurrent perineal and inguinal hernias after rectal cancer surgery., Case Description: A 51-year-old man underwent laparoscopic-assisted abdominoperineal resection for rectal cancer. About 2 months postoperatively, he developed reducible masses in the perineal and left groin regions, associated with urinary symptoms and sensation of prolapse. Physical exam revealed protruding masses that enlarged with Valsalva. Pelvic CT confirmed PH and left inguinal hernia., Interventions: Laparoscopic tension-free repair of the PH and inguinal hernia was performed on this patient. The repair was completed by the steps of adhesion separation, mesh placement, and fixation., Outcomes: The 98-minute surgery was successful without complications. The patient recovered well, ambulating on postoperative day 2 and getting discharged on day 6., Conclusion: This case demonstrates that laparoscopic tension-free repair with mesh is an effective approach for treating PH and concurrent inguinal hernia following rectal cancer surgery, resulting in successful outcomes and low recurrence rates. The laparoscopic technique provides benefits of minimal invasiveness and rapid recovery., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity, type 2 diabetes mellitus, heart failure, and non-alcoholic fatty liver disease. Polysaccharides extracted from Chinese medicine (CM) can not only alleviate pathological status but also promote health by anti-inflammatory, regulating immunity, lowering blood glucose and lipids, anti-cancer, and anti-oxidation. The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment. In addition, they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota. This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics for promoting health., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Lissencephaly is a neurodevelopmental disorder characterized by a loss of brain surface convolutions caused by genetic variants that disrupt neuronal migration. However, the genetic origins of the disorder remain unidentified in nearly one-fifth of people with lissencephaly. Using whole-exome sequencing, we identified a de novo BAIAP2 variant, p.Arg29Trp, in an individual with lissencephaly with a posterior more severe than anterior (P>A) gradient, implicating BAIAP2 as a potential lissencephaly gene. Spatial transcriptome analysis in the developing mouse cortex revealed that Baiap2 is expressed in the cortical plate and intermediate zone in an anterior low to posterior high gradient. We next used in utero electroporation to explore the effects of the Baiap2 variant in the developing mouse cortex. We found that Baiap2 knockdown caused abnormalities in neuronal migration, morphogenesis and differentiation. Expression of the p.Arg29Trp variant failed to rescue the migration defect, suggesting a loss-of-function effect. Mechanistically, the variant interfered with the ability of BAIAP2 to localize to the cell membrane. These results suggest that the functions of BAIAP2 in the cytoskeleton, cell morphogenesis and migration are important for cortical development and for the pathogenesis of lissencephaly in humans., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The anti-symmetric and anisotropic symmetric exchange interactions between two magnetic dipole moments - responsible for intriguing magnetic textures (e.g., magnetic skyrmions) - have been discovered since last century, while their electric analogues were either hidden for a long time or still not known. It is only recently that the anti-symmetric exchange interactions between electric dipoles was proved to exist (with materials hosting such an interaction being still rare) and the existence of anisotropic symmetric exchange interaction between electric dipoles remains ambiguous. Here, by symmetry analysis and first-principles calculations, we identify hafnia as a candidate material hosting the non-collinear dipole alignments, the analysis of which reveals the anti-symmetric and anisotropic symmetric exchange interactions between electric dipoles in this material. Our findings can hopefully deepen the current knowledge of electromagnetism in condensed matter, and imply the possibility of discovering novel states of matter (e.g., electric skyrmions) in hafnia-related materials., (© 2023. The Author(s).)

Background/objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life., Subjects/methods: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants ( n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry)., Results: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = -0.45, 95% CI: -0.76, -0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: -0.59, 95% CI: -0.99, -0.20) and lower isovaleric acid concentration at 3 months (mean difference: -2.12 μmol/g, 95% CI: -3.64, -0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches., Conclusions: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.

Objective: The aim of this study was to explore whether antiphosphatidylserine (aPS) antibodies play roles in the early prediction of pregnancy-induced hypertension (PIH)., Methods: The serum levels of different isotypes of aPS antibodies were compared in women diagnosed with PIH (PIH group, n  = 30) and 1 : 1 matched normotensive controls (control group, n  = 30). All patients underwent frozen embryo transfer (FET) cycles, and all serum samples were collected during 11-13 weeks of gestation. Receiver operating characteristic (ROC) curves were drawn to analyze the predictive values of aPS antibodies for PIH., Results: The women who developed PIH after FET had higher serum optical density values (450 nm) of aPS immunoglobulin (Ig) A (1.31 ± 0.43 vs. 1.02 ± 0.51, P  = 0.022), aPS IgM (1.00 ± 0.34 vs. 0.87 ± 0.18, P  = 0.046), and aPS IgG (0.50 ± 0.12 vs. 0.34 ± 0.07, P  < 0.001) compared with the normotensive controls. The serum concentration of total IgG [48.29 ± 10.71 (g/dl) vs. 34.39 ± 11.62 (g/dl), P  < 0.001] was also higher in the PIH group compared with that in the control group. The aPS IgG alone [area under the curve (AUC): 0.913, 95% confidence interval (CI): 0.842-0.985, P  < 0.001] and the combined analysis of aPS IgA, aPS IgM, aPS IgG, and total IgG (AUC: 0.944, 95% CI: 0.888-1.000, P  < 0.001) had high predictive values for PIH., Conclusion: Serum aPS autoantibody levels during the first trimester of pregnancy are positively associated with the development of PIH. Further validation is needed to clearly identify the distinct contributions and underlying mechanisms for diagnostic applications of aPS autoantibodies in PIH prediction., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Preeclampsia (PE) is a common hypertensive pregnancy disorder associated with shallow trophoblast invasion. Although bone morphogenetic protein 2 (BMP2) has been shown to promote trophoblast invasion in vitro, its cellular origin and molecular regulation in placenta, as well as its potential role in PE, has yet to be established. Additionally, whether BMP2 and/or its downstream molecules could serve as potential diagnostic or therapeutic targets for PE has not been explored., Methods: Placentas and sera from PE and healthy pregnant women were subjected to multi-omics analyses, immunoblots, qPCR, and ELISA assays. Immortalized trophoblast cells, primary cultures of human trophoblasts, and first-trimester villous explants were used for in vitro experiments. Adenovirus expressing sFlt-1 (Ad Flt1)-induced PE rat model was used for in vivo studies., Findings: We find globally decreased H3K27me3 modifications and increased BMP2 signalling in preeclamptic placentas, which is negatively correlated with clinical manifestations. BMP2 is derived from Hofbauer cells and epigenetically regulated by H3K27me3 modification. BMP2 promotes trophoblast invasion and vascular mimicry by upregulating BMP6 via BMPR1A-SMAD2/3-SMAD4 signalling. BMP2 supplementation alleviates high blood pressure and fetal growth restriction phenotypes in Ad Flt1-induced rat PE model., Interpretation: Our findings demonstrate that epigenetically regulated Hofbauer cell-derived BMP2 signalling enhancement in late gestation could serve as a compensatory response for shallow trophoblast invasion in PE, suggesting opportunities for diagnostic marker and therapeutic target applications in PE clinical management., Funding: National Key Research and Development Program of China (2022YFC2702400), National Natural Science Foundation of China (82101784, 82171648, 31988101), and Natural Science Foundation of Shandong Province (ZR2020QH051, ZR2020MH039)., Competing Interests: Declaration of interests We declare that none of the authors have any conflicts of interest with the content of this manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: This study is a systematic review of characteristics and influencing factors of nonsuicidal self-injury behavior among adolescents with depressive disorder in China. PubMed, CNKI, WanFang Database, and VIP were searched for studies. Meta-analysis was performed using RevMan 5.1 software. Nineteen studies involving 707 subjects were included in the meta-analysis. Age, gender, only child or not, and residence were included in the analysis, of which age ( I2 = 0%, p = 0.42) and residence ( I2 = 0%, p = 0.84) were analyzed by fixed-effects model; gender ( I2 = 75%, p = 0.003) and only child or not ( I2 = 50%, p = 0.140) were analyzed by random-effects model. The evidence shows that, according to the common self-injury mode and location, the nonsuicidal self-injury behavior of young people with depressive disorder aged 15-18 years is paid attention to and guided, so as to achieve early detection and early diagnosis and treatment, and reduce the occurrence of serious harm., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients., Methods: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared., Results: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE ( P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved ( P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar., Conclusions: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events., (© 2023 JGC All rights reserved; www.jgc301.com.)

Bovine lactoferrin (LF) per 1 g was reacted with 0.16, 0.32, and 0.64 mg CuCl 2 to reach 10%, 20%, and 40% copper-saturation, respectively, aiming to assess their anti-inflammatory activities to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The macrophages treated with CuCl 2 at 0.051 μg/mL dose did not have obvious change in cell viability, lactate dehydrogenase (LDH) release, and intracellular reactive oxygen species (ROS) production. However, LF and Cu-fortified LF products (10-80 μg/mL doses) mostly showed inhibitory effects on the stimulated macrophages dose-dependently. Moreover, Cu-fortified LF products of lower Cu-fortifying levels at lower doses exerted weaker inhibition on the stimulated macrophages than LF, leading to higher cell viability but decreased LDH release. Meanwhile, LF and Cu-fortified LF products at 10 and 20 μg/mL doses showed different activities to the stimulated cells, via partly decreasing or increasing the production of inflammatory mediators namely prostaglandin E 2 (PGE 2 ), nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and ROS production, depending on the used Cu-fortifying and dose levels. Compared with LF, Cu-fortified LF product (Cu-fortifying level of 0.16 mg/g LF) at 10 μg/mL dose showed enhanced inhibition on the production of PGE 2 , ROS, IL-1β, and TNF-α, evidencing increased anti-inflammatory activity. However, the inhibition of Cu-fortified LF product (Cu-fortifying level of 0.32 mg/g LF) at 20 μg/mL dose on the production of these inflammatory mediators was mostly reduced. It is thus proposed that both Cu-fortifying and dose levels could affect LF's anti-inflammatory activity in LPS-stimulated macrophages, while the Cu-fortifying level of LF could govern activity change., 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., (© 2023 The Authors.)

BACKGROUND We aimed to investigate the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with peritoneal lavage for the treatment of severe acute pancreatitis. MATERIAL AND METHODS We retrospectively reviewed data from 52 patients with severe acute pancreatitis between January 2014 and December 2021 at Jiangyin People's Hospital. The patients were divided into 2 groups: CRRT (n=26) and CRRT in combination with peritoneal lavage (n=26). The following results and outcomes were retrospectively compared: procalcitonin, interleukin-6, and C-reactive protein levels, duration of systemic inflammatory response, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, length of hospital stay, inpatient hospital costs, incidence of complications, and mortality. RESULTS There were significant differences in interleukin-6 and procalcitonin levels and APACHE-II scores after 3 and 7 days of treatment. The duration of systemic inflammatory response, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, and length of hospital stay were considerably shorter in the combination group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combination group than in the CRRT group (P<0.01). However, incidence of complications and mortality showed no significant differences between the 2 groups. CONCLUSIONS CRRT combined with peritoneal lavage is an important adjuvant therapy in the early stages of acute severe acute pancreatitis and has better clinical efficacy than CRRT alone.

Background: Hepatocellular carcinoma (HCC) is an aggressive tumor with limited treatment options, and it is the third leading cause of cancer-related deaths. Hence, novel therapeutic strategies are required to treat HCC. Eupatorium chinense L. is a traditional Chinese medicine (TCM) that can effectively neutralize heat and smoothen the flow of "Qi" through the liver. However, the anti-HCC effects of Eupatorium chinense L. remain unknown., Purpose: The present study investigated the anti-HCC effects and the underlying mechanisms of the electrophilic sesquiterpenes isolated from E. chinense L. (EChLESs) in the regulation of ferroptosis and apoptosis in HCC cells., Study Design/methods: Cell viability was assessed by the MTT assay. Cell apoptosis was confirmed by flow cytometry and western blotting assay. Ferroptosis was assessed by flow cytometry, transmission electron microscopy, and western blotting assay. Ferritinophagy was detected by acridine orange staining and western blotting assay. Small interfering RNA of nuclear receptor coactivator 4 (NCOA4) was used to confirm the role of ferritinophagy in the therapeutic effect of EChLESs on HCC cells. A mouse xenograft model was constructed to determine the inhibitory effect of EChLESs on HCC in vivo., Results: EChLESs induced apoptosis by disrupting mitochondrial membrane potential depolarization and mitochondrial reactive oxygen species. EChLESs induced ferroptosis as noted by a significant increase in mitochondrial disruption, lipid peroxidation, and intracellular iron level and decreased glutathione level. The apoptosis inhibitor Z-VAD-FMK and lipid reactive oxygen species scavenger ferrostatin 1 attenuated EChLESs-induced cell death. NCOA4-mediated ferritinophagy through autophagic flux was the crucial pathway for ferroptosis induced by EChLESs. NCOA4 knockdown alleviated EChLESs-induced cell death. EChLESs controlled the expression of NCOA4 at the transcriptional and post-transcriptional levels. In the in vivo experiment, EChLESs suppressed HCC growth in the xenograft tumor mouse model., Conclusion: EChLESs enhances cell apoptosis through mitochondrial dysfunction and ferroptosis through NCOA4-mediated ferritinophagy. Thus, Eupatorium chinense L. could be a potential TCM for treating HCC., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Objective: Preeclampsia (PE) is a common but serious pregnancy complication that adversely affects both maternal and fetal health. However, the mechanisms of its pathogenesis remain unclear, and effective biomarkers for early diagnosis are still lacking., Methods: In this retrospective study, comprehensive bioinformatic analysis and logistic regression analysis were used to compare profiles of 48 serum cytokines in 27 PE patients with those in 41 normotensive pregnant subjects., Results: The results revealed that serum cytokine profiles accumulated to different levels between the two groups, which had significant correlations with the clinical features of PE. Nine cytokines with high discriminatory capacity for diagnosising PE (AUC ≥ 0.7) were selected for inclusion in a multivariate logistic regression model for PE and calculated as a probability diagnostic formula. This model constructed from the panel of nine cytokines had better diagnostic performance than any individual cytokine (AUC = 0.97, 95% CI 0.94-1.00, P < 0.0001), with a sensitivity of 96.30% and a specificity of 90.24%., Conclusions: The set of cytokine profiles and risk assessment model described here can serve as a basis for developing early clinical diagnostic and therapeutic strategies for PE., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Severe periodontitis is the main cause of tooth loss in adults, with varying degrees of horizontal and vertical alveolar bone loss. In view of the complex alveolar bone defect, a suitable surgery planning should be made on the basis of fully nuderstanding the characteristics of alveolar bone defect in severe periodontitis and the key points of bone augmentation technique, so as to choose an appropriate method for reconstruction of alveolar bone and complete the implantation and restoration to ensure the integrity of dentition, which are important for the long-term stability of periodontal health. Based on clinical experiences and literature review, we summarizes the characteristics of alveolar bone loss in patients with severe periodontitis and the timing of implant placement after bone augmentation surgery, in order to provide reference for implant treatment of severe periodontitis.

Ischemic stroke is a common issue that severely affects the human health. Between the central nervous system and the enteric system, the " Gut-Brain " axis, the bidirectional connection involved in the neuro-immuno-endocrine network, is crucial for the occurrence and development of ischemic stroke. Ischemic stroke can lead to change in the gut microbiota and gastrointestinal hormones, which will then reversely affect the disease development. Traditional Chinese Medicine (TCM) has unique advantages with reference to the treatment for ischemic stroke. The latest research revealed that a significant portion of medicines and prescriptions of TCM exert their therapeutic effects by improving the gut microbiota and regulating the secretion of gastrointestinal hormones. The present review summarized the Chinese medicines that play a therapeutic role in cerebral ischemia through regulating the "Gut-Brain" axis and described the corresponding mechanisms. This study attempts to provide reference for clinical selection of Chinese medicines and helps better understand the relevant mechanisms of action., Competing Interests: Declaration of interest All authors declare that No conflict of interest exists., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Carpal tunnel syndrome (CTS) is a common compression neuropathy of the median nerve in the wrist. Early diagnosis of CTS is essential for selecting treatment options and assessing prognosis. The current diagnosis of CTS is based on the patient's clinical symptoms, signs, and an electromyography (EMG) test. However, they have some limitations. Recently, ultrasound has been adopted as an adjunct diagnostic tool for electromyography (EMG). Ultrasound is a non-invasive and cost-effective technique. It provides a dynamic display of morphological changes in the median nerve and an assessment of CTS etiology such as tenosynovitis, mass compression, and tendon disease. This study aimed to investigate the value of conventional ultrasound and real-time shear wave elastography (SWE) in evaluation of median neuropathy in patients with carpal tunnel syndrome (CTS) before and after surgery., Methods: First, the Boston Carpal Tunnel Questionnaire (BCTQ) was administered to patients with CTS. All subjects were measured at three levels: the distal 1/3 of the forearm, the carpal tunnel inlet, and the distal carpal tunnel using conventional ultrasound and SWE. Median nerve parameters were examined in patients with CTS 1 week after surgery., Results: The cross-sectional area (CSA) and stiffness of the median nerve at the carpal tunnel inlet and distal carpal tunnel were significantly higher in patients with CTS than in healthy controls ( p < 0.001). The CSA and stiffness of the median nerve at the carpal tunnel inlet were statistically significantly significantly between pre- and postoperative patients with CTS ( p < 0.001). The CSA and stiffness of the nerve in patients with CTS had a positive correlation with electrophysiology severity., Conclusions and Discussion: Conventional ultrasound and elastography are valuable in the diagnosis of CTS and are useful in the clinical assessment of patient's nerve recovery after operation., 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 © 2022 Wu, Zhao, Xue, Wang, Zhang and Wang.)

Objective: To investigate the effect of visual acupotomy intervention on intervertebral disc degeneration, nucleus pulposus cell apoptosis and expression of apoptosis related proteins in rabbits with cervical spondylosis (CS), so as to explore its mechanism underlying improvement of CS., Methods: A total of 48 male New Zealand rabbits were randomly divided into blank control, model, acupotomy and medication (meloxicam) groups, with 12 rabbits in each group. The neck type CS model was established by forcing the rabbit to make a neck flexion for 5 hours in a restrained chamber, once daily for 12 weeks. Rabbits of the medication group received an intramuscular injection of meloxicam (0.35 mg/kg), once daily for 4 consecutive weeks, and those of the acupotomy group received ultrasound-guided acupotomy intervention, once a week for 4 weeks. The pain threshold (PT) was measured by using a VonFrey electronic pain detector. The levels of prostaglandin E2 (PGE2), 5-hydroxytryptamine (5-HT) and substance P (SP) in serum were detected by ELISA. The severity of intervertebral disc degeneration was observed by using magnetic resonance imaging (MRI) and given scores in accordance with Suzuki's and colleague's "new classification system of cervical disk degeneration". The apoptosis of nucleus pulposus cells was analyzed by TUNEL staining. The protein expression levels of apoptosis-related protein Fas, cysteinyl aspartate-specific protease-3 (Caspase-3), B-cell lymphoma-2 asso-ciated X protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) were measured by Western blot., Results: Compared with the blank control group, the PT and Bcl-2 expression and MRI score were significantly down-regulated ( P <0.01, P <0.001), whereas the contents of serum PGE2, 5-HT and SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax were considerably up-regulated ( P <0.001, P <0.05, P <0.01) in the model group. In contrast to the model group, both the medication and acupotomy groups had an obvious increase in the levels of PT and Bcl-2 expression and MRI score ( P <0.05, P <0.01), and a significant decrease in the contents of serum PGE2, 5-HT, SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax proteins ( P <0.05). No significant differences were found between the medication and acupotomy groups in all the indexes mentioned above ( P >0.05)., Conclusion: Visual acupotomy intervention can mitigate the pain state of CS rabbits, which may be related to its functions in improving the intervertebral disc degeneration, reducing inflammatory reactions and apoptosis of nucleus pulposus cells.

Alpha fetoprotein (AFP) is a growth factor and a signaling molecule that promotes the development of HCC. However, the mechanism of the awakening of AFP in course of HCC progression remains unclear. We have studied the structure of AFP 5'-flanking regulatory sequence using dual-luciferase reporter vectors with fragments of this region. Reporter constructs were transfected into HepG2 and PLC hepatoma cell lines. The AFP 5'-flanking regulatory sequence between -1871 and -1004 bp was promoting gene transcription, while the effects of the sequence between -1004 and -667 bp were small. The fragment located between positions -667 and -448 bp inhibited the transcriptional activity of the AFP gene, while the fragment located between -448 and -287 bp promoted expression of AFP. The effects of the adjacent promoter sequence were small. A variety of transcription factor binding sites were mapped.

The aim of our study was to investigate waist circumference (WC) change and the risk of incident chronic obstructive pulmonary disease (COPD) among Chinese adults. A total of 8164 participants aged > 18 years who attended health examinations with repeat measurements of WC and lung function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 )] from 2010 to 2019 were recruited. WC change was categorized as ≤  - 2.5%, - 2.5 to 2.5%, 2.5% to 5% and > 5% according to sex. Modified Poisson regression models were used to assess the association of WC gain and the risk of COPD. During the 10-year follow-up, a total of 917 COPD cases were identified. From baseline to follow-up, the mean FEV 1 decreased from 3.20 to 2.79L among male participants and 2.28-1.95L among female participants. Compared with participants who did not have abdominal obesity, at either, baseline or follow-up, participants with abdominal obesity of both sexes after the follow-up were associated with a greater risk of COPD regardless of abdominal obesity at baseline. The risk of incident COPD increased 19% among male participants (RR = 1.19, 95%CI = 1.04-1.48) and 14% among female participants (RR = 1.14, 95%CI = 1.01-1.40) when WC gain increased > 5% during the 10-year follow-up. The COPD risk decreased 18% among male participants with a WC change ≤  - 2.5% (RR = 0.82, 95%CI = 0.67-0.99). The risk of incident COPD was positively associated with increasing WC among Chinese adults of both sexes., (© 2022. The Author(s).)

Centrosymmetric antiferromagnetic semiconductors, although abundant in nature, seem less promising than ferromagnets and ferroelectrics for practical applications in semiconductor spintronics. As a matter of fact, the lack of spontaneous polarization and magnetization hinders the efficient utilization of electronic spin in these materials. Here, we propose a paradigm to harness electronic spin in centrosymmetric antiferromagnets via Zeeman spin splitting of electronic energy levels-termed as the spin Zeeman effect-which is controlled by an electric field. By symmetry analysis, we identify 21 centrosymmetric magnetic point groups that accommodate such a spin Zeeman effect. We further predict by first principles that two antiferromagnetic semiconductors, Fe&#95;{2}TeO&#95;{6} and SrFe&#95;{2}S&#95;{2}O, are excellent candidates showcasing Zeeman splittings as large as ∼55 and ∼30  meV, respectively, induced by an electric field of 6  MV/cm. Moreover, the electronic spin magnetization associated to the splitting energy levels can be switched by reversing the electric field. Our Letter thus sheds light on the electric-field control of electronic spin in antiferromagnets, which broadens the scope of application of centrosymmetric antiferromagnetic semiconductors.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Ischemic stroke is a highly disabling and potentially fatal disease. After ischemic stroke, autophagy plays a key regulatory role as an intracellular catabolic pathway for misfolded proteins and damaged organelles. Mounting evidence indicates that astrocytes are strongly linked to the occurrence and development of cerebral ischemia. In recent years, great progress has been made in the investigation of astrocyte autophagy during ischemic stroke. This article summarizes the roles and potential mechanisms of astrocyte autophagy in ischemic stroke, briefly expounds on the crosstalk of astrocyte autophagy with pathological mechanisms and its potential protective effect on neurons, and reviews astrocytic autophagy-targeted therapeutic methods for cerebral ischemia. The broader aim of the report is to provide new perspectives and strategies for the treatment of cerebral ischemia and a reference for future research on cerebral ischemia., 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 © 2022 Su, Zhai, Wang, Zhang, Wang, Ma, Han, Wu, Yu, Zhao and Wang.)

As sediment is an essential component of rivers, the enrichment of heavy metals in sediment presents a serious threat to the aquatic environment. Many industrial cities are located along the Yellow River, and heavy metal pollution is a prominent problem in these areas. Thus, the study of heavy metal pollution in sediments of the Yellow River basin is of vital significance to the safety of the Yellow River basin ecosystem. In this study, we collected data on the concentrations of heavy metals (Pb, Cd, Cr, As, Zn, Cu, Ni, and Hg) in the sediments of the Yellow River basin from 2000 to 2020. We first analyzed the spatial distribution characteristics of heavy metals based on descriptive statistics and geostatistics and then used the Monte Carlo method to evaluate the probability of the ground accumulation index( I geo ), potential ecological risk, and toxicity units. Finally, the number of pollution sources and their contribution rates were determined by combining the positive definite matrix factor (PMF) decomposition model and Pearson correlation analysis. It was found that the mean values of ω (Pb), ω (As), ω (Zn), ω (Ni), ω (Cu), ω (Hg), ω (Cr), and ω (Cd) in the Yellow River basin sediments were 26.92, 11.78, 87.17, 31.13, 24.96, 0.07, 73.36, and 0.58 mg·kg -1 , which exceeded the mean soil background values in the Yellow River basin provinces by 1.27, 1.08, 1.26, 1.05, 1.09, 2.32, 1.14, and 5.95 times, respectively, among which Cd exceeded the standard by the largest factor and should be taken seriously. The I geo was ranked as Cd>Hg>Cr>Cu>Pb>Zn>As>Ni, and Cd and Hg showed medium-severe pollution. The proportions of heavy ecological risk in sediments in the upper, middle, and lower reaches of the Yellow River basin were 18.6%, 15.7%, and 7.1%, respectively, with a decreasing trend. Heavy metals in the sediments of the Yellow River basin were in a low-toxicity state. The PMF-Pearson correlation analysis showed that the four sources of heavy metals in the Yellow River basin sediments were mining sources (42.2%), natural activities (38.3%), agricultural activities (11.6%), and electroplating wastewater (7.9%). The results of this study can provide a basis for developing relevant pollution prevention and control measures in the Yellow River basin.

Background: Severe autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs., Methods: In this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX)., Results: Among the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3's cost of hospitalisation is more than groups 1 and 2. Hb min <40 g/L may be a key indicative factor for initiating WBE remedy therapy as IVIG/RTX may not be effective enough in 48-72 h in those patients with refractory severe SLE-AIHA. No severe adverse effects were observed in the WBE group., Conclusions: WBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA., 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 © 2022 Jiang, Zhao, Luo, Li, Zhang, Zhao and Zuo.)