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Abstract Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of the tyrosine degradation pathway. In this study, we isolated and characterized two homologous BnaFAH genes in Brassica napus L. variant Westar, and then used CRISPR/Cas9-mediated targeted mutagenesis to generate a series of transgene-free mutant lines either with single or double-null bnafah alleles. Among these mutant lines, the aacc (bnafah) double-null mutant line, rather than the aaCC (bnaa06fah) mutant line, exhibited programmed cell death (PCD) under short days (SD). Histochemical staining and content measurement confirmed that the accumulation of reactive oxygen species (ROS) in bnafah was significantly higher than that in bnaa06fah. To further elucidate the mechanism of PCD, we performed transcriptomic analyses of bnaa06fah and bnafah at different SD stages. A heatmap cluster of differentially expressed genes (DEGs) revealed that PCD may be related to various redox regulatory genes involved in antioxidant activity, ROS-responsive regulation and calcium signaling. Combined with the results of previous studies, our work revealed that the expression levels of BnaC04CAT2, BnaA09/C09SAL1, BnaA08/C08ACO2, BnaA07/C06ERO1, BnaA08ACA1, BnaC04BIK1, BnaA09CRK36 and BnaA03CPK4 were significantly different and that these genes might be candidate hub genes for PCD. Together, our results underscore the ability of different PCD phenotypes to alter BnaFAH orthologs through gene editing and further elucidated the molecular mechanisms of oxidative stress-induced PCD in plants.

Abstract The ultra‐low frequency oscillation (ULFO) imposes an emerging stability challenge to the high proportion of hydropower grids. To suppress ULFO without reducing the primary frequency regulation of the hydro governor, a novel idea to exploit the voltage regulation effect of load is implemented. First, the additional damping controller is designed and configured in static var compensator (SVC), and the frequency analysis model considering the configuration of SVC as well as damping controller is established. Based on the model, the specific influence of SVC and controller on ULFO is analysed through eigenvalue calculation. In addition, the influence of various load models and SVC location on the damping level are further studied. Consequently, a parameter optimization design method for SVC additional damping control is proposed, it is modelled as the optimization problem of damping ratio in ULFO mode under multi‐operation conditions, which is solved by a particle swarm optimization algorithm. Finally, the effectiveness of the designed SVC additional damping controller is verified in the improved four‐machine two‐area power system and the actual power grid in China.

Abstract Distant metastases are common in most elderly patients, because elderly patients are diagnosed with advanced thyroid cancer due to delayed diagnosis. There is still few specific real-world data regarding prognosis in the elderly with differentiated thyroid cancer (DTC). The purpose of this study is to evaluate the prognostic factors and survival rate of elderly DTC patients with metastasis. This retrospective study included 14,603 elderly patients diagnosed with DTC from 2010 to 2015, including 447 patients with distant metastasis via the Surveillance, Epidemiology and End Results (SEER) database. The prognostic factors of overall survival (OS) and cancer-specific survival (CSS) in elderly DTC patients with metastasis or non-metastasis were determined by univariate and multivariate analysis. Age, primary site operation, radiotherapy, chemotherapy and tumor size are associated with OS and CSS in elderly DTC patients with distant metastasis. Compared with the patients without surgery, patients with total thyroidectomy showed significantly better OS. For the elderly DTC patients, radiotherapy was associated with improving OS and CSS. Chemotherapy increased the risk of death. For elderly DTC patients, early identification of distant metastasis, total thyroidectomy and radiotherapy are associated with better prognosis.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single‐cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17–1.15]) and could distinguish between PTC and non‐PTC tissues (AUC = 0.74 [0.70–0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial‐mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

Objective: Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain edema remain not fully understood. Our research endeavors to uncover pivotal genes and their roles in brain edema following cerebral hemorrhage, and to investigate potential treatment strategies. Methods: By analyzing intracerebral hemorrhage (ICH) and control samples using the GSE216607 and GSE206971 datasets, we identified differentially expressed genes. Cross-referencing with the KEGG database, we aligned these genes with those related to tight junctions. Extensive enrichment analysis and protein interactions were performed to examine the expression and clinical significance of the identified genes. Our study employed the C57BL/6J mouse ICH model and qRT-PCR for key gene validation. Results: Notably, VASP, HCLS1, MSN, and EZR, critical for tight junctions, showed increased expression post-ICH, emphasizing their significance in BBB upkeep and PHE progression. Drug validation indicated potential therapeutic effects of Testosterone enanthate, SELENIUM, and LY 294002 on tight junction-related genes. Conclusion: This study sheds light on the potential involvement of these genes in brain edema progression post-ICH, offering promising therapeutic targets. Further research is needed for deeper understanding.

Abstract Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process.

Abstract We recently demonstrated via experiments in hydrogels and at a single air-water interface the photomolecular effect: photons directly cleaving off water molecular clusters in the visible spectrum where bulk water has negligible absorption. To model single interface experiments, here we re-derive generalized boundary conditions for Maxwell equations by assuming a transition region of the electromagnetic fields across the interface, leading naturally to the Feibelman parameters used before to describe surface photoelectric and surface plasmon effects on metals. This generalization leads to modifications of the Fresnel coefficients and an expression for the surface absorptance that can reasonably explain trends in our single-interface experimental data on the angle and polarization dependence of the beam deflection. Our work provides further support for the existence of the photomolecular effect, suggests that surface absorption should exist in many materials, and lays a foundation for assessing the impacts of such surface absorption based on the Maxwell equations.

Abstract Engineering Kondo lattice with tailored functionality is desirable for elucidating the heavy fermion physics. We realize the construction of an artificial Kondo lattice/superconductor heterojunction by growing monolayer VSe2 on bulk 2H-NbSe2 with molecular beam epitaxy. Spectroscopic imaging scanning tunneling microscopy measurements show the emergence of a new charge density wave (CDW) phase with $$\sqrt{3}\times$$ 3 × $$\sqrt{3}$$ 3 periodicity on the monolayer VSe2. Unexpectedly, a pronounced Kondo resonance appears around the Fermi level, and distributes uniformly over the entire film, evidencing the formation of Kondo lattice. Density functional theory calculations suggest the existence of magnetic interstitial V atoms in VSe2/NbSe2, which play a key role in forming the CDW phase along with the Kondo lattice observed in VSe2. The Kondo origin is verified from both the magnetic field and temperature dependences of the resonance peak, yielding a Kondo temperature of ~ 44 K. Moreover, a superconducting proximity gap opens on monolayer VSe2, whose shape deviates from the function of one-band BCS superconductor, but is reproduced by model calculations with heavy electrons participating the pairing condensate. Our work lays the experimental foundation for studying interactions between the heavy fermion liquids and the superconducting condensate.

Abstract Background Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. Aim To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. Methods The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. Discussion A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.

Abstract Background Severe adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease. Methods A retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children’s Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated. Results 699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P 0.05), indicating that the model had strong predictive power. Conclusion In this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value.

Abstract As unmanned vehicle technology advances rapidly, obstacle recognition and target detection are crucial links, which directly affect the driving safety and efficiency of unmanned vehicles. In response to the inaccurate localization of small targets such as pedestrians in current object detection tasks and the problem of losing local features in the PointPillars, this paper proposes a three-dimensional object detection method based on improved PointPillars. Firstly, addressing the issue of lost spatial and local information in the PointPillars, the feature encoding part of the PointPillars is improved, and a new pillar feature enhancement extraction module, CSM-Module, is proposed. Channel encoding and spatial encoding are introduced in the new pillar feature enhancement extraction module, fully considering the spatial information and local detailed geometric information of each pillar, thereby enhancing the feature representation capability of each pillar. Secondly, based on the fusion of CSPDarknet and SENet, a new backbone network CSE-Net is designed in this paper, enabling the extraction of rich contextual semantic information and multi-scale global features, thereby enhancing the feature extraction capability. Our method achieves higher detection accuracy when validated on the KITTI dataset. Compared to the original network, the improved algorithm’s average detection accuracy is increased by 3.42%, it shows that the method is reasonable and valuable.

Abstract Background Anaplastic lymphoma kinase (ALK) test in advanced non‐small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real‐world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. Methods In this real‐world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)‐VENTANA‐D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. Results The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC‐VENTANA‐D5F3 revealed an intra‐hospital consistency rate of 98.2% (879/895) and an inter‐hospital consistency rate of 99.2% (646/651). IHC‐VENTANA‐D5F3 was used in 53.6%, real‐time polymerase chain reaction (RT‐PCR) in 25.4%, next‐generation sequencing (NGS) in 18.3%, and fluorescence in‐situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC‐VENTANA‐D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT‐PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). Conclusions This study highlights the real‐world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC‐VENTANA‐D5F3 with high consistency and distinct clinicopathological features in ALK‐positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision‐making in NSCLC.

Abstract Objectives Subjective wellbeing has been defined as an individual’s personal appraisal of their quality of life. Subjective wellbeing is associated with positive health behaviours and improved coping abilities. This study aimed to investigate the subjective wellbeing of people living with multiple sclerosis (MS), using the novel Personal Wellbeing Index, and make comparisons with the general population. Methods Cross-sectional data was obtained from the Australian Multiple Sclerosis Longitudinal Study and the How Is Your Life Australian general population study in August-October 2020. Subjective wellbeing was measured as life satisfaction using the Personal Wellbeing Index. This instrument measures life satisfaction globally and in seven life domains, allowing the importance of domain-specific life satisfaction to be explored. Descriptive and multivariable regression analyses were conducted. Results One thousand six hundred eighty-three MS and 1,021 general population participants entered the study (mean age 52.4 and 58.6; female 79.9% and 52.4%, respectively). For people living with MS the most important life domains were standard of living and achieving in life. The domain of personal health was more influential for people living with MS (p

Objective The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins. Methods An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs. Results In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test. Conclusion STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.

To solve the contradiction between reducing water-insoluble content and maintaining high viscosity in the preparation of modified guar gum for oilfield fracturing fluid, in this work, sodium 3-chloro-2-hydroxypropylsulfonate was used as a modifier to prepare sulfonated guar gum. Orthogonal and single-factor extrapolation experiments were conducted to explore the effects of reaction conditions and the optimal process was determined as follows: reaction temperature of 26 oC, reaction time of 2.0 h, sodium hydroxide as a mass fraction of guar gum of 1.0%, and sodium 3-chloro-2-hydroxypropyl sulfonate dosage as a mass fraction of guar gum of 0.5%. Furtherly, the temperature stability, filtration property, and inhibition of formation clay of the sulfonated products were investigated. The results showed that the apparent viscosity of 0.6% solution of guar gum was increased by 33%, the water-insoluble content was decreased by 0.42%, and the temperature stability, filtration resistance, and clay inhibition were all improved. Especially, the viscosity of cross-linked sulfonated guar gum is 100% higher than that of unmodified guar gum. The structure of sulfonated guar gum was characterized and confirmed by infrared spectrum, DSC, thermogravimetric, and elemental analysis.

Abstract Research impact is an important manifestation of research competence and the focus of medical education. This study is dedicated to exploring the relationships between coauthorship networks and the research impact of Chinese medical doctoral students from a social capital perspective. A total of 16291 scientific papers from 237 doctoral students and 126 mentors at Chinese universities were selected from databases, and a study dataset including 19 variables was constructed. Nine independent variables were defined and obtained through coauthorship network analysis, and the doctoral students’ research impact, as the only dependent variable, was used to test the hypothesized relationships among the variables. The results show that the betweenness centrality, student-mentor coauthorship count and the partnership ability index significantly affect the h-index. Specifically, the coauthorship unit count plays the most important role in developing centrality, which, in turn, produces a higher h-index. In addition, betweenness centrality, student–mentor coauthorship count and the partnership ability index are good predictors of the likelihood of doctoral students entering the greater research impact group and especially improving their betweenness centrality. Specifically, doctoral students whose partnership ability index is greater than 2, student-mentor coauthorship count is greater than 4, coauthorship unit count is greater than 6, and betweenness centrality is greater than 0.02 are considered to have greater research impact. These findings suggest that the important roles of cooperation in the development of research competence and good mentorship in the acquisition of social capital by doctoral students should be emphasized. Several strategies are advised for harnessing social capital rooted in doctoral students’ coauthorship network for relevant organizations, mentors and doctoral students who want to increase medical doctoral students’ research impact.

Abstract There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Multi-targeted tyrosine kinase inhibitor QLNC-3A6 Di-maleate, a structurally novel small molecule compound, has therapeutic efficacy for the treatment of canine cutaneous mast cell tumor (CMCT) caused by mutations in the c-Kit gene. Since pharmacokinetic (PK) information plays an important role in the development and application of new drugs, etc., a rapid, highly sensitive and selective UHPLC-MS/MS analytical method was developed and validated for the first time in this study for the quantitative detection of QLNC-3A6 in canine plasma. 100 µL of plasma was precipitated using 350 µL of acetonitrile, and Chromatographic separation was performed on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 µm) at a flow rate of 0.4 mL/min, the mobile phases were set to 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile (B). The calibration curve linear range was 0.5–100 ng/mL (R2>0.99). The intraday and interday precision values (relative standard deviation, RSD) were 2.06–13.57% and 6.90–9.14%. Intraday and interday accuracies were −10.73 to 9.54% and −3.86 to 0.70% respectively. The dilution integrity RSD value and stability RSD value were less than 3.77 and 7.45%, respectively. Subsequently, the pharmacokinetics were investigated in canine after oral administration of QLNC-3A6 Di-maleate tablets at a dose of 3 mg/kg BW using this method. The results showed that QLNC-3A6 showed fast absorption rate, rapid distribution and slow metabolic elimination in canine plasma. The results of the main PK parameters including λz, T1/2λz, Cmax, Tmax and AUClast were 0.07 ± 0.01/h, 11.00 ± 2.57 h, 50.88 ± 31.94 ng/mL, 9.08 ± 11.57 h and 836.48 ± 230.53 ng h/mL, respectively.

Pancreatic pseudocysts have a high amylase concentration and are surrounded by a fibrous capsule without a true epithelial lining. They are most frequently located in the peripancreatic region, and rarely extend into the mediastinum. We report a case of a 46-year-old male patient with a history of pancreatitis due to eat and drink too much presented with nausea and vomiting, MRI of the abdominal demonstrated a cystic mass connecting the abdominal cavity to posterior mediastinum and compressing the heart and stomach, ultrasound-guided aspiration of the cystic mass revealed high levels of amylase, conffrming that the mass was a rare pancreatic pseudocyst extending into the mediastinum. He was admitted for expectant management and was successfully treated with cystojejunostomy. This case aims to illustrate the possibility of rare pancreatic pseudocysts when a cystic mass is found that penetrates the abdominal and thoracic cavities.

Abstract Background Excavation of key molecules can help identify therapeutic targets and improve the prognosis of pancreatic cancer. This study evaluated the roles of SUMO3 in cell viability, glycolysis, gemcitabine (GEM) sensitivity, and the antitumor activity of butyric acid (BA) in pancreatic cancer. Methods The mRNA and protein levels of SUMO3 were detected by qRT-PCR, Western blot, and immunohistochemical assay. SUMO3 was silenced or overexpressed in pancreatic cancer cells with or without Wnt/β-catenin pathway inhibitor, glycolysis inhibitor, GEM, or BA treatment. Cell viability was measured using the Cell Counting Kit-8 assay. Glycolysis was measured by determining the extracellular acidification rate, ATP level, and lactate content. Apoptosis was measured by flow cytometry, and TUNEL staining was used to examine in vitro and in vivo sensitivity to GEM chemotherapy. Luciferase reporter and chromatin immunoprecipitation assays were conducted to detect the binding of the SUMO3 promoter and NF-κB p65. Results SUMO3 was increased and associated with poor survival in pancreatic cancer. SUMO3 knockdown decreased cell viability and glycolysis in vitro and inhibited tumor growth in vivo. SUMO3 overexpression increased cell viability and glycolysis in vitro through the β-catenin pathway. SUMO3 knockdown increased GEM sensitivity, whereas SUMO3 overexpression decreased GEM sensitivity and inhibited the antitumor activity of BA. BA promoted histone acetylation and p-IκBα expression to inhibit NF-κB p65-mediated SUMO3 transcription. Conclusion SUMO3 acted as an active molecule in cell survival and growth by enhancing glycolysis in response to either GEM or BA. The mechanism was related to the constitutive IκBα/NF-κB/SUMO3/β-catenin signaling pathway.

The success of gangue support in roof cutting and retaining roadway depends on the evolution process of gangue side and its lateral pressure distribution. Based on the engineering background of Xinghua Coal Mine, this paper analyzes the mechanical characteristics of gangue compaction, the roof caving process, and the gangue side evolution process through indoor experiments and similar simulations. The mechanical model is established through theoretical analysis, and the impact of different factors on the lateral pressure of the gangue side is analyzed. The numerical simulation gives the distribution law of the overburden pressure and the lateral pressure of the gangue side at the boundary of the goaf and gives the gangue side support scheme from the perspective of gangue side lateral pressure influencing factors. The research results show that : ①The lateral pressure of the gangue side is related to the evolution process of the gangue in the goaf. In the self-organizing adjustment stage of the gangue, the lateral pressure of the gangue side is mainly generated by the self-weight of the gangue, and the lateral pressure depends on the accumulated height. In the passive compaction stage of gangue, the gangue body is repeatedly compacted under periodic roof pressure, and the lateral pressure of the gangue side gradually increases. In the stable stage of gangue, the gangue body is compacted at this stage, which plays an obvious supporting role in the overburdened rock. The stable value of the overburden pressure is 3.81 MPa, and the stable value of the gangue side lateral pressure is 2.12 MPa. ②From the position of the roof of the roadway to the position of the floor, the lateral pressure of the gangue side gradually increases. ③From the perspective of the external environment, the lateral pressure of the gangue side has a significant positive correlation with the roof overburden pressure and a significant negative correlation with the roof cutting angle. From the perspective of the gangue’s mechanical properties, the gangue side’s lateral pressure and the gangue’s internal friction angle show a significant positive correlation. Consequently, the “bag + net + u-shaped steel + inclined support monomer” gangue retaining support scheme is proposed, and the field application effect is good. This study may provide a reference for similar engineering conditions of gangue support.

The emergence of battery electric buses (BEBs) can alleviate environmental problems caused by tailpipe emissions in transit system. However, the high cost of on-board batteries and range anxiety hinder its further development. Recently, the advent of dynamic wireless power transfer technology (DWPT) has become a potential solution to promote the development of BEBs. Hence, this study focuses on the application of DWPT in flex-route transit system. A mixed integer non-linear model is proposed to simultaneously optimise the bus routing and the selection of corresponding bus types considering the constraints of passengers’ travel time, battery size and bus capacity. The objective is to minimise both transit agency cost and passengers’ travel time cost. A tangible hybrid variable neighbourhood search (HVNS) consisting of simulated annealing (SA) and variable neighbourhood search (VNS) is developed to solve the proposed model efficiently. Compared with GAMS (DICOPT solver) and VNS, the proposed algorithm can considerably improve computational efficiency. The results suggest that the proposed model can effectively determine the BEBs’ routing and bus type for flex-route transit system powered by DWPT through a case study in Xi’an China. A comparative analysis shows the proposed model takes 12.97% less total cost than the alternative model with terminal charging technology (TCT).

Abstract Background Pulmonary abscesses resulting from epididymitis caused by extended spectrum β-lactamase-producing hypervirulent Klebsiella pneumoniae (ESBL-hvKp) in a nondiabetic patient are extremely uncommon. The infection caused by this disseminated drug-resistant bacteria, which is generally considered an intractable case, poses a potential challenge in clinical practice. Case presentation In this case report, we present the clinical course of a 71-year-old male patient with epididymitis, who subsequently developed cough and dyspnea following anti-infection treatment. Imaging examinations revealed severe pneumonia and pulmonary abscess. The infection of ESBL-hvKp in the epididymis led to bacteremia and subsequent lung lesions. Due to poor response to anti-infection therapy, the patient required an extended duration of anti-infection treatment and ultimately chosed to discontinue treatment. Conclusions Acute epididymitis caused by ESBL-hvKP infection can result in the spread of the infection through the bloodstream, leading to severe pneumonia and lung abscess. Given the critical condition of the patient, even with active anti-infection treatment, there is a risk of treatment failure or potentially fatal outcomes.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract Background The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation. Methods The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman’s correlation analysis was used to analyse the correlation between DEGs and clinical indicators. Results Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P

Abstract We introduce a novel approach to compute Compton amplitudes involving a fermion pair inspired by Hopf algebra amplitude constructions. This approach features a recursive relation employing quasi-shuffle sets, directly verifiable by massive factorization properties. We derive results for minimal gauge invariant color-kinematic numerators with physical massive poles using this method. We have also deduced a graphical method for deriving numerators that simplifies the numerator generation and eliminates redundancies, thus providing several computational advantages.

Abstract Background The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression, but the underlying cellular and molecular mechanisms remain unclear. Implicated in depression regulation, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is investigated here to examine its role in mediating the rapid antidepressant response. Methods The onset of antidepressant response was assessed through depression-related behavioral paradigms. The signaling mechanism of PACAP in the hippocampal dentate gyrus (DG) was evaluated by utilizing site-directed gene knockdown, pharmacological interventions, or optogenetic manipulations. Overall, 446 mice were used for behavioral and molecular signaling testing. Mice were divided into control or experimental groups randomly in each experiment, and the experimental manipulations included: chronic paroxetine treatments (4, 9, 14 d) or a single treatment of ketamine; social defeat or lipopolysaccharides-injection induced depression models; different doses of PACAP (0.4, 2, 4 ng/site; microinjected into the hippocampal DG); pharmacological intra-DG interventions (CALM and PACAP6-38); intra-DG viral-mediated PACAP RNAi; and opotogenetics using channelrhodopsins 2 (ChR2) or endoplasmic natronomonas halorhodopsine 3.0 (eNpHR3.0). Behavioral paradigms included novelty suppressed feeding test, tail suspension test, forced swimming test, and sucrose preference test. Western blotting, ELISA, or quantitative real-time PCR (RT-PCR) analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus. Results Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression, and intra-DG blockade of PACAP attenuated the onset of the antidepressant response. The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors. Conversely, a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice. Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses, while optogenetic inhibition induced depression-like behaviors. The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses. Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinase II (CaMKII)-eukaryotic elongation factor 2 (eEF2) and activating the mammalian target of rapamycin (mTOR). Pre-activation of CaMKII signaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor (BDNF) signaling. Finally, acute ketamine treatment upregulated hippocampal PACAP expression, whereas intra-DG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response. Conclusions Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKII inhibition-governed eEF2-mTOR-BDNF signaling.

Abstract Background This study aimed to translate and culturally adapt the Assessment of Quality of Life (AQoL)-6D into Malay (Malay-AQoL-6D), and assesses the instrument’s acceptability, reliability, and validity among Malaysians living with chronic heart failure (HF). Methods The translation and cross-cultural adaptation process adhered to international guidelines. The Malay-AQoL-6D underwent content and face validity assessments via expert review, and pretesting among healthy individuals and patients with chronic conditions. Subsequent psychometric validation utilised clinico-sociodemographic data and paired AQoL-6D and EQ-5D-5L data from a health-related quality-of-life (HRQoL) survey involving Malay-speaking patients with HF, which encompassed assessments of Malay-AQoL-6D acceptability, internal consistency and test-retest reliability, as well as its construct, concurrent, convergent and divergent, and known-group validity. Results The Malay-AQoL-6D was deemed acceptable among clinicians and local patients, achieving a 90.8% completion rate among 314 patients surveyed. The instrument demonstrated strong content validity (item-level content validity index [CVI]: 0.83–1.00, average CVI: 0.98), internal consistency (Cronbach’s alpha: 0.72–0.89; MacDonald’s omega: 0.82–0.90, excluding the Senses dimension), and test-retest reliability (average intraclass correlation coefficients: 0.79–0.95). Confirmatory factor analysis confirmed the instrument’s two-level, six-factor structure (Satorra-Bentler [SB]-scaled χ2(df: 164): 283.67, p-value

Grasslands are the predominant land use type in China, which is currently encountering significant desertification issues. Consequently, restoring grassland vegetation has important implications for terrestrial carbon (C) levels and, consequently, the global C balance. This study focused on Salix cupularis, the primary plant used for desert control on the eastern edge of the Qinghai-Tibet Plateau. We analysed the rhizosphere and non-rhizosphere soil up to the depth of 60 cm after Salix cupularis growth for 0-24 years, examining soil total organic carbon (TOC) and its labile fractions. Following restoration, there was a gradual increase in TOC and its labile fractions, with the most significant changes observed in the rhizosphere soil at a depth of 0-20 cm. After 24 years of restoration, the TOC content in both rhizosphere and non-rhizosphere soil had increased by 141.74% and 39.44%, respectively. Labile organic C in the rhizosphere soil increased more rapidly and pronouncedly compared with the TOC. Specifically, dissolved organic C and easily oxidised organic C in the rhizosphere soil saw substantial increases of 211.03% and 217.65%, respectively. Meanwhile, compared with the 4 years of restoration, soil C pool management index of the 8-24 years soils increased, ranging from 15.70% to 132.21%. Therefore, long-term vegetation restoration on the eastern margin of the Qinghai-Tibet Plateau can significantly enhance TOC and its labile fractions, as well as improve soil C sink capacity and quality.

Abstract Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001–2002, 2011–2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2–Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment.

Abstract Objective To explore the application effect of mini clinical evaluation exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in the standardized training of general practitioners in community clinics. Methods From June 2022 to June 2023,20 general practitioners who received standardized training for residents in the general outpatient department of Changqing Community Health Service Center of Wuhan Fourth Hospital were collected as the research objects. Mini-CEX combined with DOPS was used to evaluate the general practitioners at the time of admission, 2 weeks of training and 4 weeks of training, and the results were fed back. Results The scores of 20 general practitioners at 2 weeks and 4 weeks of training were compared with the scores at the time of admission, and the difference was statistically significant, p

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Abstract Background Minimally invasive treatments for spinal cord tumours are common. The aim of this study was to compare the perioperative outcomes of patients with thoracic extramedullary spinal tumours (TEST) treated by microendoscopic minimally invasive surgery—hemilaminectomy through a homemade tubular retractor (MIS-TR) and microscopic full laminectomy (open surgery). Methods Between February 2016 and February 2021, 51 patients with TEST were included. According to their clinical data, patients were classified into the MIS-TR group (n = 30) and the open surgery group (n = 21) and assessed. Results In both groups, the mean operation time, change in perioperative ASIA score, and modified Macnab score were comparable. The average postoperative hospital stay in the MIS-TR group was substantially shorter than that in the open surgery group (p

Abstract Purpose Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. Methods Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. Results We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p

Abstract Polymeric thermal switches that can reversibly tune and significantly enhance their thermal conductivities are desirable for diverse applications in electronics, aerospace, automotives, and medicine; however, they are rarely achieved. Here, we report a polymer-based thermal switch consisting of an end-linked star-shaped thermoset with two independent thermal conductivity tuning mechanisms—strain and temperature modulation—that rapidly, reversibly, and cyclically modulate thermal conductivity. The end-linked star-shaped thermoset exhibits a strain-modulated thermal conductivity enhancement up to 11.5 at a fixed temperature of 60 °C (increasing from 0.15 to 2.1 W m−1 K−1). Additionally, it demonstrates a temperature-modulated thermal conductivity tuning ratio up to 2.3 at a fixed stretch of 2.5 (increasing from 0.17 to 0.39 W m−1 K−1). When combined, these two effects collectively enable the end-linked star-shaped thermoset to achieve a thermal conductivity tuning ratio up to 14.2. Moreover, the end-linked star-shaped thermoset demonstrates reversible tuning for over 1000 cycles. The reversible two-way tuning of thermal conductivity is attributed to the synergy of aligned amorphous chains, oriented crystalline domains, and increased crystallinity by elastically deforming the end-linked star-shaped thermoset.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. ObjectiveTo study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. MethodsPatients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. ResultsThere was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. ConclusionThe metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Abstract Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value

Abstract Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 μM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 = 0.89 ± 0.13 μM), respectively.

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Abstract To evaluate the effect of different decalcification solutions on the immunohistochemical staining of trichorhinophalangeal syndrome type 1 (TRPS1), and to provide a reliable basis for the accurate diagnosis of bone metastasis of breast cancer. Due to the limited biopsy samples of bone metastatic cancer, 20 cases of invasive breast cancer were selected to simulate bone metastatic biopsy, dividing into four groups: undecalcified group, 30% formic acid group, 10% hydrochloric acid group and 10% nitric acid group. Immunohistochemical staining was performed after treatment for 2, 6, 18 and 24 h. There was no change in the proportion and intensity of TRPS1 cells in the formic acid decalcification group within 18 h, but decreased significantly after 24 h. The staining intensity of TRPS1 and the proportion of stained cells were significantly decreased in the hydrochloric acid decalcification group since 2 h treatment. The percentage and intensity of positive cells in the nitric acid decalcification group changed little or no change within 6 h, and then gradually decreased with the extension of time. Another three invasive breast cancer samples were used to compare the effects of different decalcification solutions on the same case. In brief, we conclude that the effect of 30% formic acid decalcification on TRPS1 staining is small when the time is less than 18 h. 10% nitric acid decalcification should be controlled within 6 h, which has little effect on TRPS1 staining, and 10% hydrochloric acid decalcification will lead to significantly less positive TRPS1 staining, so it is not recommended for breast bone metastasis tissue decalcification.

Hydrochar, a carbonaceous material produced through hydrothermal carbonization of lignocellulosic biomass, has gained significant attention due to its versatile applications in agriculture, energy, and environmental protection. This review extensively explores hydrochar production by hydrothermal carbonization, specifically microwave and supercritical water treatment. These innovative approaches hold substantial promises in enhancing the efficiency and sustainability of hydrochar synthesis. The review commences with an in-depth analysis of the fundamental principles governing hydrochar production, emphasizing the distinct mechanisms of microwave and supercritical water treatment. Insightful discussions on the influence of critical process parameters, such as temperature, pressure, and residence time, underscore these factors’ pivotal role in tailoring hydrochar characteristics. Drawing on a wide array of research findings, the review evaluates the impact of different lignocellulosic biomass feedstocks on hydrochar properties, which is crucial for optimizing hydrochar production. The comparative assessment of microwave and supercritical water treatment sheds light on their unique advantages and challenges, guiding researchers toward informed decision-making in selection of methods. Furthermore, the review delves into the myriad applications of hydrochar, spanning soil amendment, carbon sequestration, and renewable energy. Environmental considerations and life cycle assessments associated with microwave and supercritical water treatment are also explored, providing a holistic perspective on the sustainability of hydrochar production. In conclusion, this comprehensive review synthesizes current knowledge on hydrochar production from diverse lignocellulosic biomass sources, emphasizing the efficacy of microwave and supercritical water methods.

Abstract Background Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. Results Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. Conclusions Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.

Objectives The etiology of flatfoot and cavus foot is multicausal and controversial. So far, no literature reports the relationship between the sagittal morphology of subtalar joint and the alignment of foot. The purpose of this study was to explore whether the subtalar alignment would influence the configuration of foot. Methods From January 2017 to January 2020, we included 109 feet in the flatfoot group, 95 feet in the cavus group, and 104 feet in the control group in this retrospective comparative study. The Gissane angle and calcaneal posterior articular surface inclination angle represented the sagittal morphology of the subtalar joint. Meary's angle, calcaneal pitch angle, and talar pitch angle reflected the alignment of foot. They were measured in the weightbearing foot X‐rays. The angles in different groups were compared via Mann–Whitney U test. We calculated the correlation between the sagittal alignment of subtalar joint and the alignment of foot using Spearman's correlation analysis. Interobserver and intraobserver reliability were calculated. Results The Gissane angle, calcaneal posterior articular surface inclination angle, Meary's angle, talar pitch angle, and calcaneal pitch angle were significantly different in the three groups. The Gissane angle had an excellent correlation with the Meary's angle (r = 0.850, p

Abstract The increasing application of TA2 titanium profiles in marine and petrochemical industries has spurred in a growing demand for diverse forms, including U‐shaped, rectangular, and tubular thin‐walled profiles. Traditional methods like mechanical subtractive processing and extrusion, despite their prevalence, suffer from high production costs and low efficiency. As a metal sheet forming technology, roll forming stands out for its efficiency, accuracy, and capability of producing complex shapes continuously. Nevertheless, the application of cold rolling to TA2 profiles is challenging primarily due to its low elastic modulus and high yield strength. In view of this, this study employed finite element simulation to analyze the stress and strain distribution during the TA2 roll forming process, aiming to have a better understanding of edge wave defect formation mechanism. Orthogonal experiments were performed to assess the influence of frame spacing, forming speed, roll gap, and downhill amount, on edge wave defects. The findings revealed a predominant influence of the downhill amount. Maintaining the downhill volume at 0.6 times the tube diameter kept the longitudinal strain below 0.9%, effectively mitigating edge wave defects. Implementation of these optimized parameters in an actual TA2 roll forming process confirmed the reliability of the simulations. This study establishes a solid foundation for advancing the TA2 tube cold roll forming process, enhancing the production efficiency of titanium profiles, and shedding some light on current energy conservation and emission reduction.

Summary: Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls. Injection of TEVs into mice impairs macrophage-mediated bacterial clearance, increases systemic bacterial dissemination, and enhances sepsis score in a PD-L1-dependent manner. Mechanistically, TEV-packaged PD-L1 inhibits Bruton’s tyrosine kinase/PLCγ2 signaling-mediated cytoskeleton reorganization and reactive oxygen species generation, impacting bacterial phagocytosis and killing by macrophages. Neutralizing PD-L1 markedly normalizes macrophage-mediated bacterial clearance in tumor-bearing mice. Importantly, circulating sEV PD-L1 levels in patients with tumors can predict bacterial infection susceptibility, while patients with tumors treated with αPD-1 exhibit fewer postoperative infections. These findings identify a mechanism by which cancer cells dampen host innate immunity-mediated bacterial clearance and suggest targeting TEV-packaged PD-L1 to reduce bacterial infection susceptibility in tumor-bearing conditions.

Background: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. Methods: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. Results: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. Conclusion: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

High-quality land-use/land-cover mapping with optical remote sensing images yet presents significant work. Even though fully convolutional semantic segmentation models have recently contributed to popular solutions, the lack of annotation data may lead to severe degradations in their inference performance. Besides, the category confusion in high-resolution representations will further exacerbate the adverse effects. In this paper, we propose a category-sensitive semi-supervised semantic segmentation framework to address these weaknesses by employing massive unlabeled data. With the perturbations from adopted hybrid data augmentation structures, we first focus on the output space and execute regularization constraints to learn category-specific discriminative features. It is formulated with a consistency self-training procedure where a dynamic class-balanced threshold selection scheme is proposed to provide high-confident pseudo supervisions for each category. In addition, we introduce pixel-wise contrastive learning on the common embedding space from both labeled and unlabeled data domains to further facilitate the semantic dependencies among category features, in which the reliable labels are leveraged as guidance for pixel sample selection. We verify the proposed framework on two benchmark land-use/land-cover datasets, and the experimental results demonstrate its competitive performance to other state-of-the-art semi-supervised methods.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.