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Abstract Background To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. Methods Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. Results A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P

Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients.Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05.Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively.Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.

BackgroundThe survival time of patients with early pancreatic cancer (PC) is still disappointing, even after surgical resection. PC has an extremely poor prognosis. Herein, we aimed to investigate the survival effect of postoperative radiotherapy (PORT) on resected stage I to II PC.Material and methodsA large eligible sample of patients was identified from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) registry. Survival analysis was conducted to evaluate the efficiency of PORT. Propensity score matching (PSM) analysis was used to reduce selection bias and to make the groups comparable.ResultsA total of 3219 patients with resected stage I to II PC was included after rigid screening. The median overall survival (OS) was 26 months with PORT (n = 1055) versus 21 months with non-PORT (n = 2164) before matching (pConclusionAddition of PORT to the treatment of patients with resected stage I to II PC conveys a survival benefit, particularly among those with N-positive or stage IIB disease.

This study demonstrated the feasibility and advantages of a hybrid, volumetric arc therapy technique that used two 90° coplanar arcs and two three-dimensional conformal tangential beams in the simultaneous-integrated boost radiotherapy of left-sided breast cancer after breast-conserving surgery. A total of nine patients with stage I, left-sided breast cancer who underwent breast-conserving surgery were selected for this retrospective study. For each patient, a hybrid arc plan was generated and then compared with two hybrid intensity-modulated radiotherapy plans. All plans were optimized using the same objectives and dose constraints. The prescription dose was 50.4 Gy to the planning target volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28 fractions. The differences among these hybrid plans were analyzed by the Kolmogorov–Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans achieved the clinical requirements of target dose coverage and normal tissue (NT) dose constraints. It was found that the hybrid arc plans showed advantages in the conformity index of the expanded gross target volume, the V5of the heart, the D2of the left ventricle, and the D2and V50.4of NTs. The average beam-on time and monitor units of the hybrid arc plans were significantly lower (P < 0.001).

Total knee arthroplasty (TKA) is a well‐established treatment for end‐stage knee osteoarthritis. However, in patients with concomitant extra‐articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra‐articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra‐articular deformities.

Abstract Background The impact of extra-articular deformities (EADs) on lower limb alignment and collateral ligament integrity during total knee arthroplasty (TKA) poses significant challenges, increasing surgical complexity. Our study aims to evaluate the influence of EADs on mechanical axis alignment and the risk of collateral ligament injury during TKA using an AI-assisted surgical planning system, with the goal of minimizing ligament damage through precise and scientific planning. Methods A healthy volunteer underwent CT and MRI scans of the lower limbs. The scan images were imported into Mimics 20.0 software, and the reconstructed models were spatially aligned using 3-maticResearch 11.0 software. Using Unigraphics NX9.0 software, 50 three-dimensional models of femoral lateral joint deformities with varying positions and angles were created. Finally, TKA was simulated using the AI JOINT preoperative planning system. Results The larger the deformity angle and the closer it is to the knee joint, the more pronounced the deviation of the mechanical axis. During MA-aligned osteotomy, nine types of deformities can damage the collateral ligaments. After adjusting the varus/valgus of the prosthesis within a safe range of 3° and leaving a residual 3° varus/valgus in the lower limb alignment, only the 25° varus and 25° valgus deformities located at 90% of the femoral anatomical axis remain uncorrected. Conclusion For patients with osteoarthritis and concurrent EAD undergoing TKA, using reconstructed 3D models of the collateral ligaments for preoperative planning helps visually assess collateral ligament damage, providing a practical solution. Minimizing intra-articular osteotomies within a safe range and allowing some residual alignment deviation can reduce the risk of collateral ligament injury.

Abstract Topological superconductors hosting Majorana zero modes are of great interest for both fundamental physics and potential quantum computing applications. In this work, we investigate the transport properties of the intrinsic magnetic topological insulator MnBi2Te4 (MBT). In normal transport measurements, we observe the presence of chiral edge channels, though with deviations from perfect quantization due to factors such as non-uniform thickness, domain structures, and the presence of quasi-helical edge states. Subsequently, we fabricate superconducting junctions using niobium leads on MBT exfoliated flakes, which show an onset of supercurrent with clear Josephson coupling. The interference patterns in the superconducting junctions reveal interesting asymmetries, suggesting changes in the magnetic ordering of the MBT flakes under small applied magnetic fields. Moreover, the modulation of the critical current by magnetic field reveals a SQUID-like pattern, suggesting the presence of supercurrent through the quasi-helical edge states.

In this study, calcium-chelating casein hydrolytic peptide (CHP-Ca) was prepared by the chelation reaction between CHP, which was prepared from enzymatic hydrolysis of micelle casein, and calcium chloride at a mass ratio of 2:1. Five enzymes (flavourzyme, alcalase, trypsin, papain and neutral protease) were screened based on hydrolysis degree (DH) and calcium-chelating capacity. A mixture of flavourzyme and trypsin was found to be the best enzyme for the enzymatic preparation of CHP. Furthermore, response surface methodology (RSM) was used to optimize the enzyme hydrolysis conditions. The results showed that the optimal conditions were enzyme-to-substrate ratio 6 000 U/g, flavourzyme-to-trypsin ratio 1:1, hydrolysis time 90 min, pH 6.9, and temperature 42 ℃. The calcium chelation capacity of the peptide prepared under these conditions was (90.46 ± 0.72) μg/mg. Finally, the structural properties and formation mechanism of CHP-Ca were investigated by X-ray diffraction (XRD), thermogravimetry (TG), zeta potential, particle size analysis and infrared (IR) spectroscopy. The results showed that CHP-Ca bound mainly by the interaction of carboxyl, amino and phosphate groups, and the zeta potential and particle size decreased after chelation, and the structure of CHP-Ca became more compact.

The biological durability of oil palm trunk modified with 1,3-dimethylol-4,5-dihydroxyethyleneurea (DMDHEU) was tested after subsequent curing at elevated temperatures. The resistance against mold, decay fungi, and subterranean termites was examined. Dimethylol dihydroxyethyleneurea-modified OPT demonstrated improved resistance against mold and decay fungi; however, the effect was lesser on subterranean termite attacks. Oil palm trunk modified with 34% DMDHEU and cured at 160 °C exhibited the most effective reduction in mass loss due to biological degradation compared to the untreated controls. High curing temperature (> 180 °C) caused cracks and ruptured the cell walls, exposing the untreated zone of the OPT to biological attack. As a non-biocidal wood modification, homogeneous dispersion of DMDHEU with adequate concentration and curing temperature is important to fully prevent OPT degradation by wood-destroying fungi and termites. These results provide valuable information for technologists to enhance or streamline the experimental design of combined modification with DMDHEU and thermal treatment, supporting their practical goals. It is recommended to continue research on the leaching of DMDHEU-modified OPT to understand the prevailing effect of DMDHEU on the biological durability of OPT, whether it is due to cross-linking or filler dispersion.

Two different low molecular cryoprotectants were analyzed in silver carp surimi proteins during different frozen storage conditions (FTC), and a comparison was performed with a conventional cryoprotectant mixture of sucrose (4%) and sorbitol (4%) as positive control (PC). The results showed that a significant decline was noted in sulfhydryl contents (SH), an increase in carbonyl groups, and a surface hydrophobicity due to myosin and protein oxidation. Meanwhile, FTC also altered the stability of secondary and tertiary structures due to the denaturative changes in myofibrillar proteins (MP). Meanwhile, samples that incorporated KC (3%), KOG (3%), and PC showed significant stability in MP against FTC induced changes. This is due to their strong hydrophilic and hydrogen interactions. MP samples containing KOG (3%) demonstrated improved cryoprotective abilities against oxidative and structural changes. Thus, we can recommend KOG as a potential cryoprotectant for maintaining the shelf-life of fish and related products on an industrial scale.

An active chitosan (CS) film containing a nano-hydroxyapatite–tea polyphenol (HAP-TP) complex was designed and prepared. The effects of HAP-TP loading on the structural and physicochemical properties of the CS-based film were evaluated. The mechanical and thermal properties of the film were significantly improved by the resulting intermolecular interactions and formation of hydrogen bonds between HAP-TP and CS, which reduced the water vapor and oxygen permeabilities of the film by 29.78 and 35.59 %, respectively. The CS-HAP-TP film exhibited excellent slow-release behavior and antioxidant activity, with a cumulative release rate at 700 h 6.79 % lower than that of CS-TP films. The CS-HAP-TP film significantly inhibited the deterioration of semi-dried golden pompano, and thus helped to retain the taste of umami and sweet amino acids in fish samples, while reducing off-flavor generation. The film therefore shows considerable potential as an active packaging material for the preservation of semi-dried fish products.

Abstract Background Developmental dysplasia of the hip (DDH) is a common cause of childhood disability, and the incidence of DDH shows significant familial aggregation. As the genetic factors of DDH remain unknown, the correlation between five candidate single nucleotide polymorphisms (SNPs) and DDH was evaluated in the Han Chinese population of Southwest China. Methods A case‒control association study was conducted in 276 patients with DDH and 318 healthy controls. SNP genotyping in the case and control groups was performed by SNPshot and multiple PCR. SNPs were genotyped in the case and control groups by multiplex PCR. The relationship between DDH and candidate SNPs was evaluated using the χ2 test. Results The genotype distributions of rs291412 in HIBCH and rs769956 in FTCDNL1 were different between the case and control groups (P

Abstract Background Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Abstract Background The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. Methods This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. Discussion Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. Trial registration www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Maize plant architecture influences planting density and, in turn, grain yield. Most of the plant architecture-related traits can be described as organ size. We describe a miniature maize mutant, Tiny plant 4 (Tip4), which exhibits reduced size of multiple organs and exhibits a semi-dominant monofactorial inheritance characteristic. Positional cloning confirmed that a 4-bp deletion in the NAC TF with transmembrane motif 1-Like (NTL) gene ZmNTL2, denoted as ZmNTL2Δ, confers the Tip4 mutation. qRT-PCR showed that ZmNTL2 was expressed in all tested tissues. ZmNTL2 functions as a transcriptional activator and is located in both the nucleus and biomembranes. The mutation does not affect the mRNA abundance of ZmNTL2 locus, but it does result in the loss of transmembrane domain and confines the ZmNTL2Δ protein to the nucleus. Knocking out ZmNTL2 has no effect on maize organ size development, indicating that the 4-bp deletion might be a gain-of-function mutation in organ size regulation. Combining transcriptome sequencing with cytokinin and auxin content determination suggests that the decreased organ size may be possibly mediated by changes in hormone homeostasis.

Abstract The study of the outcomes of critically ill patients has been a hard stuff in the field of intensive care. To explore the relationship between changes of severity scores, bioelectrical impedance analysis (BIA) and outcomes of critically ill patients, we enrolled patients (n = 206) admitted to intensive care unit (ICU) in Jinling Hospital from 2018 to 2021 with records of BIA on the days 1- and 3- ICU. Collected BIA and clinical data including simplified acute physiology score II (SAPS II) and sequential organ failure assessment. According to the baseline and change of severity scores or phase angle (PA) values, the patients were divided into: G–G, baseline good status, 3rd day unchanged; G–B, baseline good status, 3rd day deteriorated; B–G, baseline bad status, 3rd day improved; and B–B, baseline bad status, 3rd day unchanged. According to PA, the mortality of group G–G was 8.6%, and it was greater than 50% in group B–B for severity scores. The new score combining PA and severity scores established. Multivariate logistic regression analysis revealed that PA–SAPS II score was the only independent factor for 90-day mortality (P

BackgroundAs the Internet becomes an increasingly vital source of medical information, the quality and reliability of brain tumor-related short videos on platforms such as TikTok and Bilibili have not been adequately evaluated. Therefore, this study aims to assess these aspects and explore the factors influencing the dissemination of such videos.MethodsA cross-sectional analysis was conducted on the top 100 brain tumor-related short videos from TikTok and Bilibili. The videos were evaluated using the Global Quality Score and the DISCERN reliability instrument. An eXtreme Gradient Boosting algorithm was utilized to predict dissemination outcomes. The videos were also categorized by content type and uploader.ResultsTikTok videos scored relatively higher on both the Global Quality Score (median 2, interquartile range [2, 3] on TikTok vs. median 2, interquartile range [1, 2] on Bilibili, p = 1.51E-04) and the DISCERN reliability instrument (median 15, interquartile range [13, 18.25] on TikTok vs. 13.5, interquartile range [11, 16] on Bilibili, p = 1.66E-04). Subgroup analysis revealed that videos uploaded by professional individuals and institutions had higher quality and reliability compared to those uploaded by non-professional entities. Videos focusing on disease knowledge exhibited the highest quality and reliability compared to other content types. The number of followers emerged as the most important variable in our dissemination prediction model.ConclusionThe overall quality and reliability of brain tumor-related short videos on TikTok and Bilibili were unsatisfactory and did not significantly influence video dissemination. Future research should expand the scope to better understand the factors driving the dissemination of medical-themed videos.

Background: Lumbar disc degeneration (LDD) is a prevalent condition characterized by the decreased viability and functional impairment of nucleus pulposus mesenchymal stem cells (NPMSCs). Shaoyao-Gancao decoction (SGD), a traditional Chinese medicine formula, has been used to treat LDD, but its active components and mechanisms are unclear. Methods: An integrative network pharmacology and transcriptome analysis were conducted to identify bioactive compounds in SGD that could target LDD. NPMSCs were cultured under mechanical compression as a cellular model of LDD. A rat model of annulus fibrosus needle-puncture was established to induce intervertebral disc degeneration. The effects of quercetin, a predicted active component, on alleviating compression-induced NPMSC death and LDD were evaluated in vitro and in vivo. Results: The analysis identified hypoxia-inducible factor 1-alpha (HIF1A) as a potential target of quercetin in LDD. HIF1A was upregulated in degenerated human disc samples and compression-treated NPMSCs. Quercetin treatment alleviated compression-induced oxidative stress, apoptosis, and loss of viability in NPMSCs by stabilizing HIF1A. The protective effects of quercetin were abrogated by HIF1A inhibition. In the rat model, quercetin ameliorated intervertebral disc degeneration. Conclusion: Our study identified HIF1A as a protective factor against compression-induced cell death in NPMSCs. Quercetin, a bioactive compound found in the traditional Chinese medicine formula SGD, improved the survival of NPMSCs and alleviated LDD progression by stabilizing HIF1A. Targeting the HIF1A pathway through natural compounds like quercetin could represent a promising strategy for the clinical management of LDD and potentially other degenerative disc diseases.

Abstract Marine resources are rich. In recent years, more and more people have paid attention to the development of blue food. Fish protein is one of the essential biomolecules in blue food. It is a natural emulsifier because of its natural, nontoxic, easily obtained, degradable, and good surface activity. The research and application of fish protein as an emulsifier were reviewed in this paper. The emulsifying mechanism of fish protein was discussed. The emulsifying property of fish protein was affected by natural factors (source and protein concentration) and processing environment (ion strength, temperature, and pH). The emulsifying property of fish protein was improved by ultrasound, high pressure, microgel, complexation, glycosylation, and enzyme cross‐linking. It was pointed out that future research of fish protein applications should focus on the problems of shortening the gap between laboratory and commercial; stable emulsion of fish protein is difficult to preserve and single loading. It provides a reference for the development of fish protein emulsifiers.

Background Research on the utilization of outpatient and inpatient health services and its influencing factors has been well established, but there are few studies on the utilization of preventive medical services such as health checkup by residents in China. Objective To investigate the utilization of health checkup in Chinese residents aged 45 years and above and analyze its influencing factors. Methods Using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), the population aged≥45 years was selected to calculate the rate of participation in health checkup and the number of health checkup items from 2015 to 2018. Zero-inflation negative binomial regression was used to analyze the influencing factors of the number of health checkup items attended by residents. Results A total of 17 203 samples were included in this study, with an average age of (62.4±10.0), and the participation rate of 47.73% (8 21/17 203). The top three in participation rate in health checkup were Xinjiang Uygur Autonomous Region (96.47%), Shanghai (83.67%) and Beijing (82.05%), while the bottom three were Liaoning Province (35.41%), Qinghai Province (36.55%) and Fujian Province (36.94%). Among the 8 211 people who had participated in health checkup, the average age was (64.1±9.9) years old, and the median number of health checkup items per capita was 9 (5, 12). The top three in the number of health checkup items were Beijing Municipality (14 items), Shanghai Municipality (14 items) city and Xinjiang Uygur Autonomous Region (13 items), and the bottom three were Gansu Province (7 items), Anhui Province (7 items) and Liaoning Province (7.5 items). Non-parametric test showed that the number of health checkup items in urban residents was significantly higher than that in rural areas (10 items vs. 8 items), the eastern region was significantly higher than the central (10 items vs. 8 items), western (10 items vs. 8 items) and northeast (10 items vs. 8 items) region, the western region was significantly higher than the central region (9 items vs. 8 items) (P

Abstract Background Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited. Methods New patients with biallelic NR1H4 variants from our center and all patients from literature were retrospectively analyzed. Results Three new patients were identified to be carrying five new variants. Liver phenotypes of our patients manifests as low-γ-glutamyl transferase cholestasis, liver failure and related complications. One patient underwent liver transplantation (LT) and survived, and two other patients died without LT. Nine other patients were collected through literature review. Twelve out of 13 patients showed neonatal jaundice, with the median age of onset being 7 days after birth. Reported clinical manifestations included cholestasis (13/13, 100%), elevated AFP (11/11, 100%), coagulopathy (11/11, 100%), hypoglycemia (9/13, 69%), failure to thrive (8/13, 62%), splenomegaly (7/13, 54%), hyperammonemia (7/13, 54%), and hepatomegaly (6/13, 46%). Six of 13 patients received LT at a median age of 6.2 months, and only one patient died of acute infection at one year after LT. Other 7 patients had no LT and died with a median age of 5 months (range 1.2-8). There were 8 patients with homozygous genotype and 5 patients with compound heterozygous genotype. In total, 13 different variants were detected, and 5 out of 12 single or multiple nucleotides variants were located in exon 5. Conclusions We identified three newly-diagnosed patients and five novel mutations. NR1H4-related PFIC typically cause progressive disease and early death. LT may be the only lifesaving therapy leading to cure.

For investigating the corrosion behavior of aluminum alloy materials in saturated NaCl solution environment and selecting suitable materials for this harsh environment, based on the actual working conditions of industrial waste salt refining and recycling equipment, five common types of aluminum alloy materials of 2024, 3003, 5052, 6061 and 7075 were selected to carry out short-term and long-term corrosion experiments in saturated NaCl solution at 70 ℃, 80 ℃, 90 ℃, 100 ℃ and 110 ℃, respectively. The corrosion morphology and corrosion products were analyzed by X-ray diffraction(XRD), scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS) and other methods. Results indicated that 6061 possessed excellent corrosion resistance in both short-term and long-term corrosion, the corrosion products of aluminum alloy materials were mainly Al2O3 and Al(OH)3, and the corrosion types included local pitting and denudation. Moreover, the simulation predictions revealed that GM(1,1) model could reflect the change law of the aluminum alloy corrosion process well, and the corrosion degree at different times could be calculated to achieve the effect of risk prediction.

INTRODUCTION: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. METHODS: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). RESULTS: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p

Abstract Recently, the development of natural polysaccharides for ameliorating immunity and gut metabolism has attracted extensive attention. This study used Holothuria leucospilota polysaccharides (HLP) to explore the improvement mechanism in ulcerative colitis rats on perspectives of immunity and metabolism. The results showed that HLP increased goblet cells’ number and the content of tight junction proteins (zona occludens 1 and occludin) and improved intestinal barrier permeability. The levels of immune cytokines (IL‐4, IL‐6, IL‐10, IL‐18, TNF‐α, and IL‐1β) and the activity of oxidative stress‐related enzymes (superoxide dismutase, catalase, malondialdehyde, and glutathione peroxidase) were regulated. HLP regulated the related genes and proteins expression of immune cytokines, MAPK, and NLRP3 inflammasome. Furthermore, HLP treatment increased the concentration of short‐chain fatty acids (SCFAs) and regulated serum metabolic disorders by regulating amino acid metabolism, SCFA metabolism, and energy metabolism. These results provide a new perspective for developing HLP as a promising functional food for preventing and mitigating colitis.

Abstract Background Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. Methods To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. Results Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. Conclusions Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.

Mutation of the MAPK7 gene was related to human scoliosis. Mapk7 regulated the development of limb bones and skulls in mice. However, the role of MAPK7 in vertebral development is still unclear. In this study, we constructed Col2a1-cre; Mapk7f/f transgenic mouse model to delete Mapk7 in cartilage, which displayed kyphosis and osteopenia. Mechanistically, Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes, which impaired chondrocyte hypertrophy and attenuated vertebral ossification. In vivo, systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 deficiency. Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development, which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

Compared with engineering materials for earth structures subjected to prolonged, sustained hydraulic loading, the internal erosion process of widely graded loose soils (WGLS) under short-term, fluctuating hydraulic loading conditions remains insufficiently elucidated. Therefore, a novel fixed-wall permeameter is developed, capable of applying hydraulic loading at a constant flow rate and collecting effluent flowing out of specimens. A testing protocol is proposed to separate eroded silty clay particles, sandy gravel particles, and seepage water from the collected effluent. Several seepage tests are conducted on remolded specimens with various initial porosity at different inflow rates. The test results show that under a constant inflow rate, the WGLS specimens may undergo suffusion, suffosion, and stabilization stages while seeking the ultimate equilibrium state. The proposed particle migration pattern adeptly reveals the microscale mechanisms of the internal erosion phenomena observed at different stages. The inflow rate is independent of the suffusion critical hydraulic gradient but impacts the suffosion critical hydraulic gradient and internal erosion behavior following suffusion. Because hydraulic shear stress is a comprehensive indicator that considers both hydraulic gradient and initial porosity, it is more appropriate to use it to evaluate the internal stability potential of WGLS.

The synthesis of pseudo-healthy images, involving the generation of healthy counterparts for pathological images, is crucial for data augmentation, clinical disease diagnosis, and understanding pathology-induced changes. Recently, Generative Adversarial Networks (GANs) have shown substantial promise in this domain. However, the heterogeneity of intracranial infection symptoms caused by various infections complicates the model's ability to accurately differentiate between pathological and healthy regions, leading to the loss of critical information in healthy areas and impairing the precise preservation of the subject's identity. Moreover, for images with extensive lesion areas, the pseudo-healthy images generated by these methods often lack distinct organ and tissue structures. To address these challenges, we propose a three-stage method (localization, inpainting, synthesis) that achieves nearly perfect preservation of the subject's identity through precise pseudo-healthy synthesis of the lesion region and its surroundings. The process begins with a Segmentor, which identifies the lesion areas and differentiates them from healthy regions. Subsequently, a Vague-Filler fills the lesion areas to construct a healthy outline, thereby preventing structural loss in cases of extensive lesions. Finally, leveraging this healthy outline, a Generative Adversarial Network integrated with a contextual residual attention module generates a more realistic and clearer image. Our method was validated through extensive experiments across different modalities within the BraTS2021 dataset, achieving a healthiness score of 0.957. The visual quality of the generated images markedly exceeded those produced by competing methods, with enhanced capabilities in repairing large lesion areas. Further testing on the COVID-19-20 dataset showed that our model could effectively partially reconstruct images of other organs.

Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4+ or CD8+ lymphocytes were primarily the IFNγ-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by δγ T cells, and IL1β was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFNγ+ lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFNγ treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8+ T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFNγ+ CD8+ T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune responses in ACD, and recognize an indispensable role of dermal fibroblasts in shaping the development of type-1 skin inflammation through the IFNGR-CXCR3 signaling circuit during ACD pathogenesis.

BackgroundPrevious studies have explored the role of plasma proteins on osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on osteonecrosis whether a causal relationship exists and provides some evidence of causality.MethodsSummary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets.ResultsWe totally assessed the effect of 1,676 plasma proteins on osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10−5, PFDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment.ConclusionThis comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.

Objectives: Research shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset. Methods: We conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR

Background Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02–1.45); PM2.5: 1.24 (1.04–1.48); PM10: 1.30 (1.07–1.57)), wheeze (PM1: 1.27 (1.11–1.44); PM2.5: 1.30 (1.14–1.48); PM10: 1.34 (1.17–1.55)), persistent cough (PM1: 1.33 (1.06–1.66); PM2.5: 1.36 (1.09–1.71); PM10: 1.31 (1.02–1.68)) and dyspnoea (PM1: 2.10 (1.84–2.41); PM2.5: 2.17 (1.90–2.48); PM10: 2.29 (1.96–2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

The effect of acidolysis time, hydrochloric acid concentration, ozonization time and pH on the yield of indigo were investigated by single factor experiment using dried leaves of Baphicacanthus cusia (Nees) Bremek (DLB) as raw material. On this basis, the technological condition for preparing new indigo extract (NIE) by directional chemical conversion method was optimized by orthogonal experiment. Then, the physiochemical properties of NIE were analyzed by combustion assay, nitric acid assay, thin layer chromatography identification assay, moisture detection and water-soluble pigment observation assay. Moreover, UPLC-Q-TOF-MS/MS technology was utilized to compare chemical composition difference between the NIE and traditional indigo naturalis (TIN). Finally, NIE emulsion was prepared by ultrasound assisted high pressure homogenization method and its stability, antibacterial activity as well as antibacterial mechanism were evaluated. The experimental results showed that optimum process for preparing NIE were hydrochloric acid concentration of 2 %, ozonization time of 3 min, pH of 7 and acidolysis time of 1 h; Under this condition, the content and yield of indigo in the NIE were significantly improved, which could reach up to 42.6 ± 0.28 % and 2.26 ± 0.04 %, separately. NIE possessed similar physiochemical properties with TIN described in Chinese pharmacopoeia 2020, and had more diverse active ingredients than TIN. The prepared NIE emulsion demonstrated excellent stability, whether at dark or bright place, and no matter at low temperature (4 ℃) or room temperature (25 ℃), the particle size, PDI, pH and indigo content of which displayed little variation. In addition, the NIE emulsion owned good inhibitory activity against S. aureus, and its MIC and MBC values were 40 and 80 μg/mL, respectively. Moreover, NIE emulsion exhibited antibacterial effect by influencing cell membrane integrity, Ca2+-Mg2+-ATPase activity on the cell membrane and intracellular Ca2+ levels of S. aureus. All of above results will lay the foundation for the green and sustainable utilization of Baphicacanthus cusia (Nees) Bremek.

To confront the challenges posed by air pollution and climate change, China has undertaken significant initiatives to develop strategies that address both issues concurrently. However, the health benefits of these initiatives have not been clearly articulated. In this study, the dynamic changes in health impacts under air pollution and carbon reduction actions in China are evaluated by employing the latest concentration–response models and projected PM2.5 concentrations under future scenarios. From 2020 to 2060, the enforcement of clean air and climate mitigation policies is expected to increase the percentage of the population living with PM2.5 concentrations meeting the 10 μg/m3 standard by 79 %. Without the implementation of relevant mitigation measures, PM2.5-associated deaths are projected to double due to an aging population. In comparison to the 2060 reference scenario, the joint implementation of clean air and carbon neutrality measures is expected to reduce nationwide PM2.5-associated mortality by 62 %, equivalent to 2.15 (95 % CI: 1.80–2.48) million deaths. Stringent pollution controls are crucial for reducing PM2.5-associated deaths before 2030, after which carbon neutrality actions become increasingly significant from 2030 to 2060. The challenges of mitigating future PM2.5-associated deaths vary greatly across regions, showing a critical response to pollution control and carbon reduction. The research proves the effectiveness of China's future air pollution control and carbon reduction policies in mitigating PM2.5-associated deaths.

This study aimed to explore the use of Ulva lactuca polysaccharide (ULP) as a preservative for perch (Lateolabrax maculatus) fillets stored under refrigeration at 4 °C. Fresh perch fillets were treated with ULP (7–10 kDa) and potassium sorbate, respectively, to evaluate their effectiveness in inhibiting bacterial growth and maintain freshness. A 0.5% ULP solution significantly decreased the pH value, total volatile basic nitrogen value, thiobarbituric acid value, and total bacterial count of perch fillets. ULP solution delayed the changes in whiteness and texture of fillets, as well as protein degradation. The acute toxicity experiment further evaluates the safety and reliability of ULP. Simultaneously, utilizing 16S rRNA techniques, the ULP solution inhibited microorganisms known for their strong spoilage capabilities, such as Pseudomonas, Actinetobacter, and Shewanella. Microorganisms with a weaker ability to cause corruption became the dominant bacteria, such as Acetobacter, Lactobacillus, and Faecalibacterium, thereby exerting a degree of inhibition against spoilage.

Abstract Background: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S‐1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. Methods: A non‐inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. Results: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent‐to‐treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3‐year overall survival (OS) and disease‐free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153–1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064–0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076–0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110–1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. Conclusion: Adjuvant SOX was non‐inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.

In order to solve the problems of the detection of various foodborne stimulants in different animal-derived foods such as significant differences in matrix effects and many types of interference, a method was established for the determination of 10 protein anabolic agents, 8 glucocorticoids, and 12 diuretics in animal-derived foods by pass-through solid phase extraction (SPE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample was extracted with 5% formic acid in acetonitrile, and the extract was purified by pass-through solid phase extraction before being analyzed by UPLC-MS/MS. The internal standard method was used for quantification. The results showed that good linearity was observed for all analytes within their respective concentration ranges. The average recoveries ranged from 67.5% to 114.3% with relative standard deviations (RSDs) between 0.7% and 16.1% (n = 6). This method is characterized by high sensitivity, simple operation, high throughput and high detection efficiency, which improves the measurement accuracy of different complex matrices and can meet the need for the detection of the 30 foodborne stimulants in animal-derived foods used in sports events.

Abstract Background Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. Method Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. Results Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. Conclusion The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

ObjectiveTo investigate the prevalence and influencing factors of stroke in residents aged 40 years and older in Guangdong province for developing stroke prevention and control policies. MethodsTotally 21 176 permanent residents aged 40 years and older were recruited with multistage random cluster sampling in urban and rural regions of 5 municipalities in Guangdong province for a survey conducted during July – December 2020. All the participants undertook face-to-face interview with a questionnaire designed by domestic experts, physical examination and laboratory tests. Unconditional multivariate logistic regression model was used to analyze influencing factors of stroke. ResultsAmong 16 993 participants surveyed effectively, 361 stroke sufferers were identified and the crude and age-adjusted stroke prevalence were 2 124.40/100 000 and 1 725.25/100 000, respectively. Multivariate unconditional logistic regression analysis revealed following risk factors of stroke among the participants: ≥ 50 years old, smoking, lack of physical activity, family history of stroke, hypertension, diabetes, dyslipidemia, high homocysteine, and atrial fibrillation or valvular heart disease; while, being female and with an individual annual income of 5 000 – 10 000 or more than 20 000 Chinese yuan were protective factors against stroke. ConclusionThe prevalence of stroke was relatively low and influenced mainly by gender, age, annual personal income, smoking, lack of physical activity, family history of stroke, hypertension, diabetes, dyslipidemia, high homocysteine, atrial fibrillation or valvular heart disease among urban and rural residents aged 40 years and older in Guangdong province.

Abstract Background Antiviral therapy has been reported to be associated with lower recurrence rate of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV) infection. While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were both recommended as first-line therapies for HBV patients, recent retrospective studies proposed a lower incidence rate of HCC occurrence or recurrence in those receiving TDF compared ETV. However, the survival benefits of switching to TDF therapy after prolonged ETV treatment before surgery remain uncertain. We delineate the rationale and design of SWITE, a randomized, open-label, phase III trial contrasting TDF switch therapy versus ETV maintenance in HBV-related HCC patients. Methods and analysis This is a prospective, randomized, controlled, single-center study with two parallel groups of patients with HBV-related HCC who have received long-term ETV therapy before surgery. West China Hospital will enroll 238 patients, randomized in a 1:1 ratio to TDF switch therapy or ETV maintenance after surgery. The primary endpoint of this study is 3-year recurrence free survival (RFS), with the secondary endpoint being 3-year overall survival (OS) after curative surgery of HCC. Safety events will be diligently recorded. Ethics and dissemination The study protocol aligns with the ethical guidelines of the 1975 Declaration of Helsinki. It was approved by ethics committee of West China Hospital (approval number: 2022-074) and was registered with chictr.org.cn (chiCTR2200057867). Informed consent will be obtained from all participants. The results of this trial will be published in peer-reviewed journals and presentations at national and international conferences relevant to this topic. Trial registration chiCTR2200057867 . Date of registration is March 20 2022.

Abstract Most current research is devoted to electrochemical nitrate reduction reaction for ammonia synthesis under alkaline/neutral media while the investigation of nitrate reduction under acidic conditions is rarely reported. In this work, we demonstrate the potential of TiO2 nanosheet with intrinsically poor hydrogen-evolution activity for selective and rapid nitrate reduction to ammonia under acidic conditions. Hybridized with iron phthalocyanine, the resulting catalyst displays remarkably improved efficiency toward ammonia formation owing to the enhanced nitrate adsorption, suppressed hydrogen evolution and lowered energy barrier for the rate-determining step. Then, an alkaline-acid hybrid Zn-nitrate battery was developed with high open-circuit voltage of 1.99 V and power density of 91.4 mW cm–2. Further, the environmental sulfur recovery can be powered by above hybrid battery and the hydrazine-nitrate fuel cell can be developed for simultaneously hydrazine/nitrate conversion and electricity generation. This work demonstrates the attractive potential of acidic nitrate reduction for ammonia electrosynthesis and broadens the field of energy conversion.

Abstract Background Approximately 40% of patients with hormone receptor (HR)‐positive and human epidermal growth factor receptor 2 (HER2)‐negative advanced breast cancer (ABC) exhibit PIK3CA mutations. Aims This study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS‐10352, a selective PI3Kα inhibitor, in this patient population. Materials and Methods Conducted as a phase 1 dose‐escalation trial, HS‐10352 was administered orally once‐daily (QD) at dose levels of 2, 4, 6, and 8 mg. The primary endpoints were dose‐limiting toxicity (DLT) and the maximum tolerated dose (MTD). This study is registered at ClinicalTrials.gov (NCT04631835). Results Between August 2020 and March 2022, a total of 18 female patients were enrolled. DLT, manifested as hyperglycemia, occurred in two patients in the 8 mg QD group, establishing an MTD of 6 mg QD. The most common treatment‐related adverse events were hyperglycemia (88.9%) and weight loss (61.3%). In the 6 mg QD group, four patients (66.7%) had a partial response (PR), and one (16.7%) had stable disease (SD). Among the four patients with PIK3CA mutated tumors in this dosage group, three (75.0%) had PR and one (25.0%) had SD. The median progression‐free survival was not reached (95% confidence interval, 11.1‐NA). Discussion and Conclusion HS‐10352 at 6 mg QD was well‐tolerated in patients with HR‐positive, HER2‐negative ABC, and showed preliminary antitumor activity in patients with PIK3CA mutated tumors. These findings support the further clinical development of HS‐10352.

Remote sensing image (RSI) scene classification aims to identify semantic categories in RSI using neural networks. However, high-performance deep neural networks typically demand substantial storage and computational resources, making practical deployment challenging. Knowledge distillation has emerged as an effective technique for developing compact models that maintain high classification accuracy in RSI tasks. Existing knowledge distillation methods often overlook the high inter-class similarity in RSI scenes, leading to low-confidence soft labels from the teacher model, which can mislead the student model. Conversely, overly confident soft labels may discard valuable non-target information. Additionally, the significant intra-class variability in RSI contributes to instability in the model’s decision boundaries. To address these challenges, we propose an efficient method called instance-level scaling and dynamic margin-alignment knowledge distillation (ISDM) for RSI scene classification. To balance the target and non-target class influence, we apply an entropy regularization loss to scale the teacher model’s target class at the instance level. Moreover, we introduce dynamic margin alignment between the student and teacher models to improve the student’s discriminative capability. By optimizing soft labels and enhancing the student’s ability to distinguish between classes, our method reduces the effects of inter-class similarity and intra-class variability. Experimental results on three public RSI scene classification datasets (AID, UCMerced, and NWPU-RESISC) demonstrate that our method achieves state-of-the-art performance across all teacher–student pairs with lower computational costs. Additionally, we validate the generalization of our approach on general datasets, including CIFAR-100 and ImageNet-1k.

Toxoplasma gondii, a pathogenic apicomplexan parasite, infects approximately one third of the world’s population and poses a serious threat to global public health. Microneme proteins (MICs) secreted by the microneme, an apical secretory organelle of T. gondii, play important roles in the invasion, motility, and intracellular survival of T. gondii. In this study, we selected 11 genes of interest (GOIs) of T. gondii, tentative MICs predicted to be localized in micronemes, and we used the CRISPR-Cas9 system to construct epitope tagging strains and gene knockout strains to explore the localization and function of these 11 tentative MICs. Immunofluorescence assay showed that nine tentative MICs (TGME49_243930, TGME49_200270, TGME49_273320, TGME49_287040, TGME49_261710, TGME49_205680, TGME49_304490, TGME49_245485, and TGME49_224620) were localized or partially localized in the microneme, consistent with the prediction. However, TGME49_272380 and TGME49_243790 showed different localizations from the prediction, being localized in the endoplasmic reticulum and the dense granule, respectively. Further functional characterization of the 11 RHΔGOI strains revealed that deletion of these 11 GOIs had no significant effect on plaque formation, intracellular replication, egress, invasion ability, and virulence of T. gondii. Although these 11 GOIs are not essential genes for the growth and virulence of tachyzoites of type I RH strain, they may have potential roles in other developmental stages or other genotypes of T. gondii. Thus, further research should be performed to explore the possible role of the nine mics and the other two GOIs in other life cycle stages and other genotypes of T. gondii.

While Mammarenavirus Wenzhouense (WENV) is broadly distributed across Asia, the dynamics of WENV infection remain unclear. In this study, a field-derived strain of WENV was used to inoculate Sprague Dawley (SD) rats by intramuscular injection, and the process of viral infection was observed over the course of 28 d. Viral RNA became detectable in the blood at 3 dpi and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 dpi, and then began to decline by 14 d, but remained detectable in intestine and brain tissues at 21 and 28 dpi. Viral shedding was detected from fecal samples for 5 d, from 6 to 11 dpi using qRT-PCR, and was recovered from feces collected at 8 dpi. Horizontal contact infection occurred among cage-mates at 14 and 21 dpi. Antibodies against the nucleocapsid were detected at 5 dpi, and then increased and persisted until the end of the experiment. These results enabled us to determine the kinetics of viremic response, viral shedding in feces, and horizontal transmission dynamics, as well as the potential sites for WENV replication and viral maintenance in nature.

Abstract Background To date, most countries lifted the restriction requirement and coexisted with SARS-CoV-2. Thus, dietary behavior for preventing SARS-CoV-2 infection becomes an interesting issue on a daily basis. Coffee consumption is connected with reduced COVID-19 risk and correlated to COVID-19 severity. However, the mechanisms of coffee for the reduction of COVID-19 risk are still unclear. Results Here, we identified that coffee can inhibit multiple variants of the SARS-CoV-2 infection by restraining the binding of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), and reducing transmembrane serine protease 2 (TMPRSS2) and cathepsin L (CTSL) activity. Then, we used the method of "Here" (HRMS-exploring-recombination-examining) and found that isochlorogenic acid A, B, and C of coffee ingredients showed their potential to inhibit SARS-CoV-2 infection (inhibitory efficiency 43–54%). In addition, decaffeinated coffee still preserves inhibitory activity against SARS-CoV-2. Finally, in a human trial of 64 subjects, we identified that coffee consumption (approximately 1–2 cups/day) is sufficient to inhibit infection of multiple variants of SARS-CoV-2 entry, suggesting coffee could be a dietary strategy to prevent SARS-CoV2 infection. Conclusions This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era.

The shear mechanical behavior of soils in the slip zone under cyclic loading is of great importance for the stability analysis of landslides. In this paper, an experimental device is developed to study the nonlinear deformation mechanism of soil in sliding zone under cyclic load. Based on field tests and model tests, the change of shear strength parameters of the soil in the slip zone with cyclic loading parameters was investigated. Based on the deformation characteristics of slip zone soils under cyclic dynamic loading, the unsteady creep transient model based on fractional derivative is established, and three deformation types of sliding zone soil are described: stable, critical and destructive. The Levenberg-Marquardt (LM) algorithm is used to fit the nonlinear curves, and the applicability of the model is also verified. This research method provides a test apparatus and a method for studying the deformation characteristics of slip zone soils under cumulative loading.

Pinus is an economically and ecologically important genus whose members are dominant components globally in low-latitude mountainous and mid-latitude temperate forests. Pinus species richness is currently concentrated in subtropical mid-low latitudes of the Northern Hemisphere, differing from the latitudinal diversity gradient mostly recognized in woody angiosperms. How the present pattern was developing in Earth's past is still poorly studied, particularly in eastern Asia. Here, a new fossil species, Pinus shengxianica sp. nov. is described based on a fossil seed cone from the Late Miocene Shengxian Formation in Zhejiang, southeast China. A co-occurring cone is recognized as a known fossil species, Pinus speciosa Li. Extensive comparison of extant and fossil members of Pinus suggests P. shengxianica shares a striking cone similarity to Pinus merkusii and Pinus latteri (subsection Pinus) from tropical Southeast Asia in having annular bulges around the umbo on the apophysis. The morphological resemblance indicates these two extant low-latitude pines probably possess a close affinity with the present newly-discovered P. shengxianica and originated from East Asian mid-low latitude ancestors during this generic re-diversification in the Miocene. This scenario is consistent with the evolutionary trajectory reflected by the pine fossil history and molecular data, marking the Miocene as a key period for the origin and evolution of most extant pines globally. The co-occurrences of diverse conifers and broadleaved angiosperms preferring diverse niches demonstrate Late Miocene eastern Zhejiang was one of the hot spots for coniferophyte diversity and hosted a needled-broadleaved mixed forest with complex vegetation structure and an altitudinal zonation.

Abstract Edge supercurrent has attracted great interest recently due to its crucial role in achieving and manipulating topological superconducting states. Proximity-induced superconductivity has been realized in quantum Hall and quantum spin Hall edge states, as well as in higher-order topological hinge states. Non-Hermitian skin effect, the aggregation of non-Bloch eigenstates at open boundaries, promises an abnormal edge channel. Here we report the observation of broad edge supercurrent in Dirac semimetal Cd3As2-based Josephson junctions. The as-grown Cd3As2 nanoplates are electron-doped by intrinsic defects, which enhance the non-Hermitian perturbations. The superconducting quantum interference indicates edge supercurrent with a width of ~1.6 μm and a magnitude of ~1 μA at 10 mK. The wide and large edge supercurrent is inaccessible for a conventional edge system and suggests the presence of non-Hermitian skin effect. A supercurrent nonlocality is also observed. The interplay between band topology and non-Hermiticity is beneficial for exploiting exotic topological matter.