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Bo-Hao Zheng,1,2,* Zhi-Xian He,3,* Juan Zhang,4,* Jing-Jing Ma,5,* Hong-Wei Zhang,1,2 Wei Zhu,1,2 Zhi-Min Shao,6 Xiao-Jian Ni1,2 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 4Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, 200032, People’s Republic of China; 5State Key Laboratory of Reproductive Medicine, Department of Breast Surgery, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, People’s Republic of China; 6Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Cancer Center and Cancer Institute, Fudan University, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Jian NiDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64041990Email ni.xiaojian@zs-hospital.sh.cnZhi-Min ShaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Cancer Center and Cancer Institute, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64175590Email shaozhimingfd@163.comBackground: Triple-negative breast cancers (TNBC), comprising about 20% of breast cancers, have a poor prognosis. Currently, there is no effective target therapy for TNBC. LncRNA TUSC7 has been identified as a tumor suppressor in osteosarcoma and colorectal cancer. In this study, we investigated the clinical significance and the biological function of TUSC7 in breast cancer.Methods: We retrospectively evaluated the expression level and clinical significance of TUSC7 in 90 paired breast cancer tissues and normal tissues. The proliferation, migration, and invasion assays were performed to investigate the biological function of TUSC7 in breast cancer. Finally, microarray, a luciferase reporter assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the potential underlying mechanism of tumor suppressor role of TUSC7.Results: Low TUSC7 expression was found to be an independent prognostic factor of poor overall survival (OS) in TNBC patients. Ectopic expression of TUSC7 inhibited tumor cell growth both in vitro and in vivo. TUSC7 overexpression significantly promoted the sensitivity of MDA-MB-468 cells to paclitaxel and carboplatin. In terms of the mechanism, TUSC7 might perform its biological function through binding with miR-1224-3P and regulating its expression level. Besides, genes in cell cycle pathways, such as BUB3 (budding uninhibited by benzimidazoles 3) and TGF-ß (targeting transforming growth factor β) pathways were downregulated, and genes involved in the MAPK (mitogen-activated protein kinase) (TGFBR2, transforming growth factor-beta receptor 2), PI3K-AKT (phosphoinositide 3-kinase- AKT serine/threonine kinase 1) and NF-κB (nuclear factor-kappa B subunit) pathways were upregulated in TUSC7 knockdown MDA-MB-231 cells.Conclusion: The low TUSC7 expression is an independent prognostic factor of poor OS of TNBC patients. TUSC7 might inhibit breast cancer cell growth and metastasis both in vitro and vivo through binding with miR-1224-3P and regulating MAPK, PI3K/AKT, and NF-κB signaling pathways.Keywords: TUSC7, long non-coding RNA, MiR-1224-3P, triple-negative breast cancer, prognosis

Objective: To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence. Methods: This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16-93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02. Results: With a median follow-up of 63 (12-267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670-0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624-0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P <0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P <0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P >0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion: The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

The pathological hallmarks of various neurodegenerative diseases including Parkinson's disease and Alzheimer's disease prominently feature the accumulation of misfolded proteins and neuroinflammation. Chaperone-mediated autophagy (CMA) has emerged as a distinct autophagic process that coordinates the lysosomal degradation of specific proteins bearing the pentapeptide motif Lys-Phe-Glu-Arg-Gln (KFERQ), a recognition target for the cytosolic chaperone HSC70. Beyond its role in protein quality control, recent research underscores the intimate interplay between CMA and immune regulation in neurodegeneration. In this review, we illuminate the molecular mechanisms and regulatory pathways governing CMA. We further discuss the potential roles of CMA in maintaining neuronal proteostasis and modulating neuroinflammation mediated by glial cells. Finally, we summarize the recent advancements in CMA modulators, emphasizing the significance of activating CMA for the therapeutic intervention in neurodegenerative diseases., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To summarize the clinical features and outcomes of deflazacort-induced Steven Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) to raise awareness among patients with Duchenne muscular dystrophy (DMD), neurologists as well as other deflazacort users. Methods: The clinical data of a boy with DMD who had SJS induced by deflazacort treated at the Department of Rheumatology & Clinical Immunology of Tianjin Children's Hospital in July 2024 was analyzed retrospectively. Taking "deflazacort" "Steven-Johnson syndrome" "toxic epidermal necrolysis" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2024. The clinical characteristics, treatment and outcomes of deflazacort-induced SJS-TEN were summarized. Results: A 12-year-old boy was admitted with a 3-day history of rash. He was diagnosed with DMD at the age of 3 and had been treated with prednisolone since the age of 8. Forty-four days before admission, the patient started deflazacort to replace prednisolone. Three days before admission, progressively worsening erythematous maculopapular rashes, blisters and skin peeling (8% body surface area), oral mucosal erosion, and exudative conjunctivitis occurred, thus deflazacort was discontinued. Complete remission of SJS was achieved after treatment with intravenous immunoglobulin (IVIG, total 1.4 g/kg), 2 doses of etanercept (0.9 mg/kg, once), subcutaneous injection and intravenous methylprednisolone (0.7 mg/(kg·d)). Based on the literature, there were 5 reports in English while none in Chinese, altogether 7 cases were reported. All the patients were male, aged 3-45 years. Duration of deflazacort exposure was 2-8 weeks. Dermatology diagnosis of our case was SJS, and 5 cases were TEN. One patient was diagnosed with exudative erythema multiforme, and subsequent deflazacort oral challenge test was positive. Treatment included methylprednisolone or dexamethasone in 5 cases, IVIG in 6 cases, etanercept in 3 cases and cyclosporine in 1 case. All patients recovered completely. Conclusion: The synthetic corticosteroid deflazacort can cause rare but severe adverse reactions such as SJS-TEN, which needs close monitoring and prompt recognition and management.

Background: Early recognition of sepsis, a common life-threatening condition in intensive care units (ICUs), is beneficial for improving patient outcomes. However, most sepsis prediction models were trained and assessed in the ICU, which might not apply to emergency department (ED) settings., Aims: To establish an early predictive model based on basic but essential information collected upon ED presentation for the follow-up diagnosis of sepsis observed in the ICU., Study Design: This study developed and validated a reliable model of sepsis prediction among ED patients by comparing 10 different methods based on retrospective electronic health record data from the MIMIC-IV database. In-ICU sepsis was identified as the primary outcome. The potential predictors encompassed baseline demographics, vital signs, pain scale, chief complaints and Emergency Severity Index (ESI). 80% and 20% of the total of 425 737 ED visit records were randomly selected for the train set and the test set for model development and validation, respectively., Results: Among the methods evaluated, XGBoost demonstrated an optimal predictive performance with an area under the curve (AUC) of 0.90 (95% CI: 0.90-0.91). Logistic regression exhibited a comparable predictive ability to XGBoost, with an AUC of 0.89 (95% CI: 0.89-0.90), along with a sensitivity and specificity of 85% (95% CI: 0.83-0.86) and 78% (95% CI: 0.77-0.80), respectively. Neither of the five commonly used severity scoring systems demonstrated satisfactory performance for sepsis prediction. The predictive ability of using ESI as the sole predictor (AUC: 0.79, 95% CI: 0.78-0.80) was also inferior to the model integrating ESI and other basic information., Conclusions: The use of ESI combined with basic clinical information upon ED presentation accurately predicted sepsis among ED patients, strengthening its application in ED., Relevance to Clinical Practice: The proposed model may assist nurses in risk stratification management and prioritize interventions for potential sepsis patients, even in low-resource settings., (© 2024 British Association of Critical Care Nurses.)

Objectives: To observe the effect of electroacupuncture (EA) preconditioning at "Quchi" (LI11) and "Xuehai" (SP10) in prevention of urticaria., Methods: Twenty-four male SD rats were randomly divided into control, model and preconditioning of EA (Pre-EA) groups (8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days. The times of rat's scratching the sensitized skin were recorded. HE staining method was used to observe the pathological changes of skin tissue, and toluidine blue staining method was used to observe the morphology of mast cells (MCs) in the skin, blood, mesentery, and peritoneal fluid, and calculate the degranulation rate. Immunohistochemical stainning was used to detect immunoglobulin E (IgE), histamine (HIS), and 5-hydroxytryptamine (5-HT) expressions in subcutaneous tissue. NOD like receptor thermal domain associated protein 3 (NLRP3) inflammasome, apoptosis related granule protein (ASC), and cysteine aspartate aminotransferase 1 (Caspase-1) protein expression levels in skin tissue were detected by Western blot. The contents of serum interleukin(IL)-1β and IL-18 were detected using ELISA method., Results: Compared with the control group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs in skin, blood, mesentery and peritoneal fluid, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1β and IL-18 were significantly increased ( P <0.01, P <0.05) in the model group. In comparison with the model group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1β and IL-18 in EA group were significantly decreased ( P <0.01, P <0.05)., Conclusions: EA preconditioning at LI11 and SP10 can prevent and treat UR by inhibiting inflammatory response, which is related to the regulation of pyroptosis.

Direct visualization of the states originating from electron-electron interactions is of great importance for engineering the surface and interfacial properties of graphene-based quantum materials. For instance, the rotational symmetry breaking or nematic phase inferred from spectroscopic imaging has confirmed the existence of correlated states in a wide range of moiré materials. Here, we study the atomic-scale spatial distributions and symmetry of wave functions in gate-tunable twisted double bilayer graphene by employing scanning tunneling microscopy/spectroscopy and continuum model calculations. A series of spectroscopic imaging analyses are used to identify dominant symmetry breaking of the emergent states. Interestingly, in non-integer hole fillings, a completely new localized electronic state with rotational symmetry breaking is observed on the left side of the valence flat band. The degree of anisotropy is found to increase from the conduction flat band through the valence flat band to the new state. Our results provide an essential microscopic insight into the flat band and its adjacent state for a full understanding of their electric field response in twisted graphene systems.

Semihydrogenation is a crucial industrial process. Noble metals such as Pd have been extensively studied in semihydrogenation reactions, owing to their unique catalytic activity toward hydrogen activation. However, the overhydrogenation of alkenes to alkanes often happens due to the rather strong adsorption of alkenes on Pd active phases. Herein, we demonstrate that the incorporation of Pd active phases as single-atom sites in perovskite lattices such as SrTiO 3 can greatly alternate the electronic structure and coordination environment of Pd active phases to facilitate the desorption of alkenes rather than further hydrogenation. Furthermore, the incorporated Pd sites can be well stabilized without sintering by a strong host-guest interaction with SrTiO 3 during the activation of H species in hydrogenation reactions. As a result, the Pd incorporated SrTiO 3 (Pd-SrTiO 3 ) exhibits an excellent time-independent selectivity (>99.9 %) and robust durability for the photocatalytic semihydrogenation of phenylacetylene to styrene. This strategy based on incorporation of active phases in perovskite lattices will have broad implications in the development of high-performance photocatalysts for selective hydrogenation reactions., (© 2024 Wiley-VCH GmbH.)

One-dimensional (1D) van der Waals (vdW) heterotubes, where different kinds of 1D nanotubes coaxially nest inside each other, offer a flexible platform for promising applications. The various properties of these 1D heterotubes depend on their diameter. Here, we present a systematic theoretical investigation into the structural and electronic properties of two kinds of 1D transition-metal dichalcogenide (TMD) heterotubes. We demonstrate that the thermodynamic stability of 1D heterotubes is determined by their interlayer distance. Additionally, we establish that the band alignment transition changes from type I to type II in 1D TMD heterotubes. We identify two distinct transition mechanisms, originating from the exchange of either the valence band maximum or the conduction band minimum. According to an electrostatic model, the band alignment transition is attributed to the interlayer electric field effect, which depends on the heterotube diameter. The findings in this work provide valuable physical insights into the band alignment transition in 1D heterotubes and are instrumental for their potential applications in nanotechnology.

C -Alkyl glycosides, an important class of C-glycosides, are widely found in various drugs and natural products. The synthesis of C -alkyl glycosides has attracted considerable attention. Herein, we developed a Ni/photoredox catalyzed decarboxylative C ( sp 3 )- C ( sp 3 ) coupling reaction of stable glycosylcarboxylic acids with simple aliphatic bromides to generate C-alkyl glycosides. The method successfully linked several functional molecular fragments (natural products or drugs) to a sugar moiety, showing the extensive application prospects of this transformation. Controlled experiments and DFT calculations demonstrated that the reaction pathway contains a free radical process, and a possible mechanism is proposed.

Immune checkpoint inhibitors (ICIs) have become an important cornerstone of many tumour treatments. However, the toxicity profile of immune-chemotherapy combination treatment approaches among older adult cancer patients is still unclear. Patients with any cancer who received camrelizumab-based immunotherapy were eligible for inclusion. The primary endpoints were adverse events (AEs) and immune-related adverse events (irAEs), which were defined based on Naranjo's algorithm. Patients were stratified by age (≥ 70 years and < 70 years), and comparisons were made based on the type of camrelizumab-based therapy (monotherapy, combined chemotherapy, or combined anti-VEGF therapy). A total of 185 patients were administered camrelizumab-based immunotherapy, 55 (30%) of whom were ≥ 70 years old. A total of 146 (78.9%) patients received camrelizumab-based combination treatment. The incidence of all-grade AEs was 56.8% (105 patients), while that of irAEs was 36.8% (68 patients). There was no difference in the percentage of patients experiencing any grade or grade ≥ 3 AEs between age groups. However, the frequency of irAEs (both any grade and grade ≥ 3) significantly differed by age group (P = 0.001 and 0.009, respectively). The results of multivariable analysis revealed that age ≥ 70 years was the only independent risk factor for irAEs. The results of subgroup analysis revealed that the incidence of irAEs was higher in older patients treated with camrelizumab-chemotherapy, while the incidence rates were similar between age groups in the monotherapy and combination anti-VEGF treatment subgroups. Immune-related diabetes mellitus occurred more frequently among older adults. The spectrum of irAEs showed that combination immunotherapy had more widely effects on the organ system than monotherapy. In this study, older (≥ 70 years) patients had a higher risk of all-grade and high-grade irAEs when receiving camrelizumab chemotherapy combination treatment. Notably, long-term random glucose monitoring should be performed during ICI-based immunotherapy in older cancer patients., (© 2024. The Author(s).)

Lead-free halide perovskites have recently garnered significant attention due to their rich structural diversity and exceptionally ultralow lattice thermal conductivity ( κ L ). Here, we employ first-principles calculations in conjunction with self-consistent phonon theory and Boltzmann transport equations to investigate the crystal structure, electronic structure, mechanical properties, and κ L s of two typical vacancy-ordered halide perovskites, denoted with the general formula Cs 3 Bi 2 X 9 (X = Br, I). Ultralow κ L s of 0.401 and 0.262 W mK -1 at 300 K are predicted for Cs 3 Bi 2 Br 9 and Cs 3 Bi 2 I 9 , respectively. Our findings reveal that the ultralow κ L s are mainly associated with the Cs rattling-like motion, vibrations of halide polyhedral frameworks, and strong scattering in the acoustic and low-frequency optical phonon branches. The structural analysis indicates that these phonon dynamic properties are closely relevant to the bonding hierarchy. The presence of the extended Bi-X antibonding states at the valence band maximum contributes to the soft elastic lattice and low phonon group velocities. Compared to Cs 3 Bi 2 Br 9 , the face-sharing feature and weaker bond strength in Cs 3 Bi 2 I 9 lead to a softer elasticity modulus and stronger anharmonicity. Additionally, we demonstrate the presence of wave-like κ C in Cs 3 Bi 2 X 9 by evaluating the coherent contribution. Our work provides the physical microscopic mechanisms of the wave-like κ C in two typical lead-free halide perovskites, which are beneficial to designing intrinsic materials with the feature of ultralow κ L .

Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were →4)-β-D-Manp(1→, →4)-β-Glcp(1→, β-D-Manp(1→, and β-D-Glcp(1→. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1β to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.

Hepatic sinusoidal obstruction syndrome (HSOS),a toxic liver injury,can lead to multiple organ failure in severe cases and is even fatal.Early diagnosis is of great significance for the selection of treatment regimens and prognosis.Currently,ultrasound,as the preferred diagnostic method for liver diseases,has been recommended in expert consensus and criteria for the diagnosis of HSOS.However,there are no definitive imaging diagnostic standards.This paper summarizes the sonographic features of ultrasound and new ultrasound technologies in HSOS research.Analyzing the characteristic sonographic images from gray-scale ultrasonography,Doppler ultrasonography,ultrasound elastography,and contrast-enhanced ultrasonography at different stages of the disease enables the establishment and refining of the corresponding imaging diagnostic standards and provides effective auxiliary examination methods for the early diagnosis and differential diagnosis of HSOS.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer cells largely rely on aerobic glycolysis or the Warburg effect to generate essential biomolecules and energy for their rapid growth. The key modulators in glycolysis including glucose transporters and enzymes, e.g. hexokinase 2, enolase 1, pyruvate kinase M2, lactate dehydrogenase A, play indispensable roles in glucose uptake, glucose consumption, ATP generation, lactate production, etc. Transcriptional regulation and post-translational modifications (PTMs) of these critical modulators are important for signal transduction and metabolic reprogramming in the glycolytic pathway, which can provide energy advantages to cancer cell growth. In this review we recapitulate the recent advances in research on glycolytic modulators of cancer cells and analyze the strategies targeting these vital modulators including small-molecule inhibitors and microRNAs (miRNAs) for targeted cancer therapy. We focus on the regulation of the glycolytic pathway at the transcription level (e.g., hypoxia-inducible factor 1, c-MYC, p53, sine oculis homeobox homolog 1, N 6 -methyladenosine modification) and PTMs (including phosphorylation, methylation, acetylation, ubiquitination, etc.) of the key regulators in these processes. This review will provide a comprehensive understanding of the regulation of the key modulators in the glycolytic pathway and might shed light on the targeted cancer therapy at different molecular levels., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma (HNSCC) using single-cell and bulk RNA-sequencing data. Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes (DEGs) between nivolumab resistant and nivolumab sensitive patients using R software. The Least Absolute Shrinkage Selection Operator (LASSO) regression and Recursive Feature Elimination (RFE) algorithm were performed to identify key genes associated with nivolumab resistance. Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The relationships of key genes with immune cell infiltration, differentation trajectory, dynamic gene expression profiles, and ligand-receptor interaction were explored. Results We found 83 DEGs. They were mainly enriched in T-cell differentiation, PD-1 and PD-L1 checkpoint, and T-cell receptor pathways. Among six key genes identified using machine learning algorithms, only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy ( P < 0.05). The high PPP1R14A gene expression group had lower immune score ( P < 0.01), higher expression of immunosuppressive factors (such as PDCD1 , CTLA4, and PDCD1LG2 ) ( r > 0, P < 0.05), lower differentiation of infiltrated immune cells ( P < 0.05), and a higher degree of interaction between HLA and CD4 ( P < 0.05). Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients. Therefore, PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

Colorectal cancer is the most common malignant tumor of digestive tract, and the incidence of colorectal cancer in China is especially characterized by middle and low rectal cancer. In recent years, with the progress of computer science, artificial intelligence technology has developed rapidly, and has achieved a lot of application results in the medical field. At present, artificial intelligence technology has covered various stages of colorectal cancer, including screening, individualized assessment, auxiliary diagnosis and treatment decision-making, refined surgery and prognosis judgment, providing help for the accurate and individualized treatment of rectal cancer. However, the lack of standardized, systematic, and scalable AI models remains a major pain point for the field. Therefore, it is necessary to carry out large-scale prospective clinical studies on artificial intelligence model to further confirm its application value in the clinical diagnosis and treatment of rectal cancer.

Background: HALE is now a regular strategic planning indicator for all levels of the Chinese government. However, HALE measurements necessitate comprehensive data collection and intricate technology. Therefore, effectively converting numerous diseases into the years lived with disability (YLD) rate is a significant challenge for HALE measurements. Our study aimed to construct a simple YLD rate measurement model with high applicability based on the current situation of actual data resources within China to address challenges in measuring HALE target values during planning., Methods: First, based on the Chinese YLD rate in the Global Burden of Disease (GBD) 2019, Pearson correlation analysis, the global optimum method, etc., was utilized to screen the best predictor variables from the current Chinese data resources. Missing data for predictor variables were filled in via spline interpolation. Then, multiple linear regression models were fitted to construct the YLD rate measurement model. The Sullivan method was used to measure HALE. The Monte Carlo method was employed to generate 95% uncertainty intervals. Finally, model performances were assessed using the mean absolute error (MAE) and mean absolute percentage error (MAPE)., Results: A three-input-parameter model was constructed to measure the age-specific YLD rates by sex in China, directly using the incidence of infectious diseases, the incidence of chronic diseases among persons aged 15 and older, and the addition of an under-five mortality rate covariate. The total MAE and MAPE for the combined YLD rate were 0.0007 and 0.5949%, respectively. The MAE and MAPE of the combined HALE in the 0-year-old group were 0.0341 and 0.0526%, respectively. There were slightly fewer males (0.0197, 0.0311%) than females (0.0501, 0.0755%)., Conclusion: We constructed a high-accuracy model to measure the YLD rate in China by using three monitoring indicators from the Chinese national routine as predictor variables. The model provides a realistic and feasible solution for measuring HALE at the national and especially regional levels, considering limited data., (© 2024. The Author(s).)

Background: Meteorological factors are associated with various health outcomes. However, it remains uncertain whether ambient temperature affects animal aggressive behaviors and causes mammalian-related injuries (MRI) in humans. The study aimed to examine the effect of daily mean temperature on MRI in Guangzhou, China., Methods: Individual cases of MRI were obtained from Guangzhou Injury Surveillance System during 2014-2019. A combination of a distributed lag nonlinear model and conditional quasi-Poisson regression, implemented within a time-stratified case-crossover design, was employed to evaluate the association between temperature and MRI. Subgroup analyses were conducted by sex, age group, education level, and types of mammals., Result: This study included 24,206 MRI cases among which 89.7 % were caused by cats or dogs. We observed a nonlinear relationship between daily mean temperature and MRI. The impact of high temperatures was most pronounced on the current day and remained statistically significant on the next day. Compared with the reference temperature with a minimum risk of injuries (9.3 °C, approximately 2nd percentile of temperature), 75th percentile of temperature (27.4 °C) exerted the greatest relative risk (RR) of injuries (RR = 1.45, 95 % CI: 1.25-1.68) over lag 0-1 days. In subgroup analyses, the effects of high temperatures among males and females were similar. Individuals aged 15-34 years and 35-59 years were more susceptible to MRI at high temperatures compared to other age groups. The risk of injuries caused by cats or dogs consistently increased with high temperatures. We did not find significant impacts of low temperatures., Conclusion: Short-term heat exposure plays an important role in the occurrence of MRI. The findings highlight the importance of enhancing public awareness regarding the high temperature-associated hazards posed by mammals. There is a need for enhanced regulations and measures on the management for cats and dogs to mitigate the harm caused in hot seasons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing non-alcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring., Methods: Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random-effects meta-analysis to investigate the effect of GDM on NAFLD in mothers and offspring. Pooled odds ratio (OR) was calculated using hazards ratio (HR), relative risk (RR), or OR reported from each study, with corresponding 95% confidence intervals (CI), and statistical heterogeneity was assessed with the Cochran Q-test and I 2 statistic, with two-sided p values. The study protocol was pre-registered on PROSPERO (CRD42023392428)., Findings: Twenty studies pertaining to mothers and offspring met the inclusion criteria and 12 papers were included further for meta-analysis on intergenerational NAFLD development. Compared with mothers without a history of GDM, mothers with a history of GDM had a 50% increased risk of developing NAFLD (OR 1.50; 95% CI: 1.21-1.87, over a follow-up period of 16 months-25 years. Similarly, compared with offspring born to non-GDM-complicated pregnancies, offspring born to GDM-complicated pregnancies displayed an approximately two-fold elevated risk of NAFLD development (2.14; 1.57-2.92), over a follow-up period of 1-17.8 years., Interpretation: This systematic review and meta-analysis suggests that both mothers and offspring from GDM-complicated pregnancies exhibit a greater risk to develop NAFLD. These findings underline the importance of early monitoring of liver function and prompt intervention of NAFLD in both generations from GDM-complicated pregnancies., Funding: No funding was available for this research., Competing Interests: All authors declare no competing interests, or activities that could appear to have influenced the submitted work., (© 2024 The Author(s).)

Background: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients., Methods: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175)., Results: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I 2  = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I 2  = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I 2  = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (P interaction  = 0.43 and P interaction  = 0.71, respectively)., Conclusion: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The high prevalence of hepatitis A delivered a blow to public health decades ago. The World Health Organization (WHO) set a goal to eliminate viral hepatitis including hepatitis A by 2030. In 2008, hepatitis A vaccines were integrated into the Expanded Program on Immunization (EPI) in China to alleviate the burden of hepatitis A, although the effectiveness of the EPI has not been well investigated., Objective: We aimed to evaluate the intervention effect at both provincial and national levels on the incidence of hepatitis A in the Chinese mainland from 2005 to 2019., Methods: Based on the monthly reported number of hepatitis A cases from 2005 to 2019 in each provincial-level administrative division, we adopted generalized additive models with an interrupted time-series design to estimate province-specific effects of the EPI on the incidence of hepatitis A among the target population (children aged 2-9 years) from 2005 to 2019. We then pooled province-specific effect estimates using random-effects meta-analyses. We also assessed the effect among the nontarget population and the whole population., Results: A total of 98,275 hepatitis A cases among children aged 2-9 years were reported in the Chinese mainland from 2005 to 2019, with an average annual incidence of 5.33 cases per 100,000 persons. Nationally, the EPI decreased the hepatitis A incidence by 80.77% (excess risk [ER] -80.77%, 95% CI -85.86% to -72.92%) during the study period, guarding an annual average of 28.52 (95% empirical CI [eCI] 27.37-29.00) cases per 100,000 persons among the target children against hepatitis A. Western China saw a more significant effect of the EPI on the decrease in the incidence of hepatitis A among the target children. A greater number of target children were protected from onset in Northwest and Southwest China, with an excess incidence rate of -129.72 (95% eCI -135.67 to -117.86) and -66.61 (95% eCI -67.63 to -64.22) cases per 100,000 persons on average, respectively. Intervention effects among nontarget (ER -32.88%, 95% CI -39.76% to -25.21%) and whole populations (ER -31.97%, 95% CI -39.61% to -23.37%) were relatively small., Conclusions: The EPI has presented a lasting positive effect on the containment of hepatitis A in the target population in China. The EPI's effect on the target children also provided a degree of indirect protection for unvaccinated individuals. The continuous surveillance of hepatitis A and the maintenance of mass vaccination should shore up the accomplishment in the decline of hepatitis A incidence to ultimately achieve the goal set by the WHO., (©Bo-Wen Ming, Li Li, Hao-Neng Huang, Jia-Jun Ma, Chen Shi, Xiao-Han Xu, Zhou Yang, Chun-Quan Ou. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 28.02.2024.)

Background: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients., Materials and Methods: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386)., Results: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I 2  = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I 2  = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I 2  = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC., Conclusion: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events., (© 2024. The Author(s).)

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1β(IL-1β) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1β, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1β-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Laparoscopic colorectal surgery has been carried out in China for more than 30 years and has experienced a three-stage high-speed development of "exploring and designing,optimising and standardising, perfecting and re-innovating" at the technical level. Based on the support and assistance of laparoscopic technology, colorectal surgery has made rapid progress in sub-microscopic anatomy, surgical procedures, surgical concepts, instruments and equipment. Nowadays, the technology and efficacy of laparoscopic colorectal surgery have gradually reached the ceiling, and in view of the existing pain points and the future direction of development, where will we go? This article summarised the past three decades of experience and consolidate the results to guide the future practice and the way forward.

Integrin subunit α3 (ITGA3) is a member of the integrin family and interacts with extracellular matrix proteins. However, there have been few reports regarding the role of ITGA3 in papillary thyroid cancer. The expression levels of ITGA3 were firstly analyzed by bioinformatics tools and in vitro experiments, followed by evaluating its prognostic significance in papillary thyroid cancer patients using Kaplan-Meier, receiver operating characteristic, and Cox regression analyses. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted and the upstream miRNAs of ITGA3 were determined. The results showed that the ITGA3 mRNA and protein levels were higher in the papillary thyroid cancer group than those in the normal group (all P < 0.05). Moreover, ITGA3 performed well in distinguishing the recurrence-free survival (RFS) status and served as an independent prognostic factor of papillary thyroid cancer patients (P < 0.01). Besides, significant relations between ITGA3 and genetic alterations were observed (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction and cell adhesion molecules were the shared regulatory pathways. Moreover, ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b. Of note, the ITGA3 mRNA level was reduced after has-miR-199b-3p/5p was overexpressed. In conclusion, ITGA3 could be a reliable biomarker and have potential value in predicting the RFS status of papillary thyroid cancer patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Competing Interests: The authors report no conflicts of interest.

Recurrent neural networks (RNNs) are often used to model circuits in the brain and can solve a variety of difficult computational problems requiring memory, error correction, or selection (Hopfield, 1982; Maass et al., 2002; Maass, 2011). However, fully connected RNNs contrast structurally with their biological counterparts, which are extremely sparse (about 0.1%). Motivated by the neocortex, where neural connectivity is constrained by physical distance along cortical sheets and other synaptic wiring costs, we introduce locality masked RNNs (LM-RNNs) that use task-agnostic predetermined graphs with sparsity as low as 4%. We study LM-RNNs in a multitask learning setting relevant to cognitive systems neuroscience with a commonly used set of tasks, 20-Cog-tasks (Yang et al., 2019). We show through reductio ad absurdum that 20-Cog-tasks can be solved by a small pool of separated autapses that we can mechanistically analyze and understand. Thus, these tasks fall short of the goal of inducing complex recurrent dynamics and modular structure in RNNs. We next contribute a new cognitive multitask battery, Mod-Cog, consisting of up to 132 tasks that expands by about seven-fold the number of tasks and task complexity of 20-Cog-tasks. Importantly, while autapses can solve the simple 20-Cog-tasks, the expanded task set requires richer neural architectures and continuous attractor dynamics. On these tasks, we show that LM-RNNs with an optimal sparsity result in faster training and better data efficiency than fully connected networks., (© 2023 Massachusetts Institute of Technology.)

Objective: To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC)., Methods: TTK expression in PTC and normal groups were compared using TCGA data and in vitro experiments. The prognostic value of TTK and its possible role in PTC dedifferentiation was evaluated. Next, TTK involvement in PTC occurrence and progression was analyzed via in vitro experiments. Subsequently, analyses of enrichment and immune cell infiltration were conducted to reveal the possible mechanism. Finally, we predicted the target miRNAs followed by performing a luciferase reporter experiment., Results: TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis ( P < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all P < 0.05). PTC cell growth, migration, and invasion were inhibited upon TTK knockdown. Besides, TTK was involved in metabolic processes and regulated cell adhesion molecules pathway. Its overexpression was positively associated with immune cell infiltrates ( P < 0.05). Moreover, miR-582-5p was an upstream target of TTK., Conclusion: TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.

Loquat fruits are among the most popular Chinese fruits because of their unique taste and aroma. The quality profiles of these fruits during 18 days of shelf-life at 20 °C were elucidated by headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), E-nose, and E-tongue. During shelf-life period, the properties and variations of 43 (20 aldehydes, 7 esters, 6 ketones, 1 alcohol, and 1 furan) volatile flavored compounds were determined by GC-IMS, which showed that the contents of methyl 3-methyl butanoate, ethyl acetate, and dimethyl ketone gradually decrease with prolonged shelf-life time, while (E)-2-heptenal, heptanal, (E)-2-pentenal, 1-penten-3-one 3-pentanone and 2-pentylfuran increase. The PCA based on the signal intensity of GC-IMS and E-nose, revealed that loquat fruits are well distinguished at different shelf-life times. The taste profile alternates as the storage time increases, along with higher pH, and lower amounts of total soluble solids, vitamin C, and total phenolics. The visual plots of GC-IMS, E-nose, and E-tongue had good consistency, and they characterized the aroma characteristics of loquat fruits well during different shelf-life periods. The findings of this research provide a useful understanding of the flavors of loquat fruits during their prolonged shelf-life, and a potential research basis for advancements in the loquat industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Restless legs syndrome (RLS) is a common non-motor symptom in Parkinson's disease (PD), but its pathogenesis remains unclear. This study aimed to explore the potential neural substrates of RLS in a large sample of patients with PD., Methods: A total of 42 patients with PD with RLS and 124 patients with PD without RLS were prospectively recruited at our hospital between February 2019 and October 2020 and underwent structural and resting-state functional magnetic resonance imaging. Differences between the two patient groups were assessed using voxel-based morphometry and functional connectivity analysis. PD duration, Part III of the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) score, and levodopa equivalent daily dose were treated as covariates., Results: Patients with PD with RLS had significantly larger gray matter volume in the bilateral posterior cingulate cortex than patients with PD without RLS (FDR-adjusted P < 0.05). Compared to patients without RLS, those with RLS had significantly lower functional connectivity between the left central opercular cortex and the bilateral precentral gyri and postcentral gyri (FDR-adjusted P < 0.001)., Conclusion: Our study provides the first evidence that in patients with PD, RLS is associated with significantly larger gray matter volume in the posterior cingulate cortex and lower resting-state functional connectivity within the sensorimotor network. Our results may help clarify the pathophysiology of RLS in PD and identify possible therapeutic targets., (© 2022. The Author(s).)

Introduction: Pain in Parkinson's disease is poorly understood, and most patients with pain do not respond to dopaminergic drugs. We aimed to explore the mechanisms of dopa-responsive and -unresponsive pain by comparing such patients against patients without pain in terms of neural activity and functional connectivity in the brain., Methods: We prospectively examined 31 Parkinson's patients with dopa-responsive pain, 51 with dopa-unresponsive pain and 93 without pain using resting-state functional magnetic resonance imaging. Neural activity was assessed in terms of the amplitude of low-frequency fluctuation, while functional connectivity was assessed based on analysis of regions of interest., Results: Patients with dopa-unresponsive pain showed significantly higher amplitude of low-frequency fluctuation in the right parahippocampal/lingual region than patients with no pain. However, there was no amplitude difference between the dopa-responsive pain group and the no pain group. Patients with dopa-unresponsive pain also differed significantly from patients with no pain in their functional connections between the superior temporal gyrus and other areas of cerebral cortex, between amygdala and thalamus and between the amygdala and putamen. Patients with dopa-responsive pain differed significantly from patients with no pain in their functional connections between temporal fusiform cortex and cerebellum, between precentral gyrus and temporal fusiform cortex and between precentral gyrus and cerebellum., Conclusions: Regional neural activity and functional connectivity in the brain differ substantially among Parkinson's patients with dopa-unresponsive pain, dopa-responsive pain or no pain. Our results suggest that dopa-responsive and -unresponsive pain may arise through different mechanisms, which may help guide the development of targeted therapies., (© 2022. The Author(s).)

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research., (© 2023. The Author(s).)

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference ( P <0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95% CI =0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group ( n =444) and a validation group ( n =125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P <0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95% CI =0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Soil microorganisms can respond to changes in wetland ecosystem quality and functional evolution sensitively. To explore the changes and response mechanisms of soil microorganisms under ecological restoration measures, the characteristics of the soil microbial community and their influencing factors were analyzed using high-throughput sequencing technology in four different habitats (revegetation area, native vegetation area, tidal creek, and tidal flat) during the ecological restoration process in Haifeng wetland in Guangdong. The results showed that:soil physicochemical properties of the four different habitats were significantly different; the contents of TC, TN, TOC, and TK in the tidal creek were significantly higher than those in the other habitats; and the contents of TC, TN, and TP in the revegetation restoration area were significantly higher than those in the tidal flat. The EC values in the tidal creeks and tidal flat were significantly higher than those in the revegetation area and the native vegetation area. The diversity index and abundance of soil bacteria in the tidal creek were the highest, and those in the vegetation restoration area were significantly higher than those in the bare flat. The archaea in the tidal creek were significantly more complex than those in the other three habitats, and the fungal community diversity index and abundance in the native vegetation area were significantly higher than those in the other areas, which had the most complex community structure. TN and TC were the main factors affecting the bacterial community, whereas TN and EC were the main factors affecting the archaea community, and pH, TN, and TP were the key factors affecting the fungal community. In conclusion, the planting of vegetation on the tidal flat increased the diversity and richness of the soil microbial community during the process of ecological restoration, indicating that it has resulted in positive feedback on ecological restoration so far. The results of this study can provide a theoretical basis for the selection of ecological restoration strategies for the tidal flat.

Cobalt phthalocyanine anchored on carbon material has attracted an enormous amount of attention due to its superior performance in electrocatalytic CO 2 reduction. However, the interaction between cobalt phthalocyanine and the carbon substrate remains problematic, and the role of intrinsic carbon defects is unfortunately ignored in the anchoring of cobalt phthalocyanine on carbon. Herein, new interactions between the bridging N atoms of cobalt phthalocyanine and the edge defects of carbon have been discovered, which result in a novel model of anchoring of cobalt phthalocyanine on ketjen black carbon. Such anchored cobalt phthalocyanine has been found to be responsible for superior catalysis for electrochemical reduction of CO 2 to CO with high selectivity and low overpotential.

Endometriosis is a common chronic inflammatory and estrogen-dependent disease that mostly affects people of childbearing age. The dietary inflammatory index (DII) is a novel instrument for assessing the overall inflammatory potential of diet. However, no studies have shown the relationship between DII and endometriosis to date. This study aimed to elucidate the relationship between DII and endometriosis. Data were acquired from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. DII was calculated using an inbuilt function in the R package. Relevant patient information was obtained through a questionnaire containing their gynecological history. Based on an endometriosis questionnaire survey, those participants who answered yes were considered cases (with endometriosis), and participants who answered no were considered as controls (without endometriosis) group. Multivariate weighted logistic regression was applied to examine the correlation between DII and endometriosis. Subgroup analysis and smoothing curve between DII and endometriosis were conducted in a further investigation. Compared to the control group, patients were prone to having a higher DII (P = 0.014). Adjusted multivariate regression models showed that DII was positively correlated with the incidence of endometriosis (P < 0.05). Analysis of subgroups revealed no significant heterogeneity. In middle-aged and older women (age ≥ 35 years), the smoothing curve fitting analysis results demonstrated a non-linear relationship between DII and the prevalence of endometriosis. Therefore, using DII as an indicator of dietary-related inflammation may help to provide new insight into the role of diet in the prevention and management of endometriosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes., Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes., Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated., Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm 2 , 24.09 ± 4.58 versus 28.66 ± 4.27; p  < 0.001), CNBD (no./mm 2 , 28.22 ± 11.11 versus 37.37 ± 12.76; p  = 0.015), and CNFL (mm/mm 2 , 13.11 ± 2.79 versus 16.17 ± 2.37; p  < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p  = 0.019) and CNFL (OR = 1.7060, p  = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832., Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

The VEGF receptor is mock-coupled with a known active compound and the active groups of the inhibitor which can bind to VEGF were analyzed. Using asiatic acid as a lead compound, 10 novel skeleton candidate compounds were designed through introduction of the active groups onto the special location and synthesized simultaneously. Furthermore, the structure of these compounds was determined by 1 H NMR, 13 C NMR and MS and 9 compounds were identified as the new compounds. Moreover, the in vitro anti-tumor activities of these new compounds were determined by MTT assay on two cancer cell lines (HepG2 and SGC-7901). The results showed that compounds I 1 and II 2 have more potent anticancer activity than positive control drugs such as gefitinib and paclitaxel.

High-temperature body-centered cubic (BCC) γ-U is effectively stablized by γ-(U,Zr) alloys that also make it feasible to use it as a nuclear fuel. However, relatively little research has focused on γ-(U,Zr) alloys due to their instability at room temperature. The effect of Zr composition on its mechanical properties is not clear yet. Herein, we perform molecular dynamics simulations to investigate the mechanical and dynamical stabilities of γ-(U,Zr) alloys under high temperatures, and we calculate the corresponding lattice constants, various elastic moduli, Vickers hardness, Debye temperature, and dynamical structure factor. The results showed that γ-U, β-Zr, and γ-(U,Zr) are all mechanically and dynamically stable at 1200 K, which is in good agreement with the previously reported high-temperature phase diagram of U-Zr alloys. We found that the alloying treatment on γ-U with Zr can effectively improve its mechanical strength and melting points, such as Vickers hardness and Debye temperature, making it more suitable for nuclear reactors. Furthermore, the Zr concentrations in γ-(U,Zr) alloys have an excellent effect on these properties. In addition, the dynamical structure factor reveals that γ-U shows different structural features after alloying with Zr. The present simulation data and insights could be significant for understanding the structures and properties of UZr alloy under high temperatures.

Industry dominates energy consumption and carbon emissions in China, and industrial energy efficiency is critical for the achievement of energy transformation and carbon emission reduction. With the rapid development of the digital economy, its impact on energy efficiency is gradually emerging, and it is necessary to clarify the influencing mechanism on industrial energy efficiency. Based on the panel data of industrial sectors in 41 cities in the Yangtze River Delta from 2011 to 2019, the main objectives of this study are to more accurately measure the industrial total factor energy efficiency in each city by using the Super-Dynamic-SBM model. It analyses the influence mechanism of the digital economy and other influencing factors on industrial total factor energy efficiency with different methods. The research results indicate that, first, the total factor energy efficiency of the industrial sector in the Yangtze River Delta urban agglomeration generally showed a steady upward trend. Second, the digital economy and environmental regulation play a significant role in promoting total factor energy efficiency. In addition, industrial energy efficiency and the digital economy show an inverted "U" shaped relationship. With the improvement of the digital economy, its marginal contribution to total factor energy efficiency gradually weakens. Finally, technological progress is an important transmission channel for the impact of the digital economy on total factor energy efficiency., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson's disease (PD), but its neuropathology remains elusive. Our goal is to explore the potential neural substrates of EDS in a large sample of individuals with PD., Methods: We recruited 48 PD patients with and 87 PD patients without EDS. We used resting-state functional magnetic resonance imaging to compare amplitudes of low-frequency fluctuations (ALFF) between the two groups. We also explored functional connectivity (FC) between the entire brain and regions where ALFF differed between the two groups as well as FC between selected regions of interest. Age, Part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) score and use of dopamine receptor agonists were treated as covariates in the comparisons., Results: EDS was associated with significantly lower ALFF in the left angular gyrus, and ALFF in this region correlated negatively with score on the Epworth Sleepiness Scale in patients with PD. EDS was also associated with significantly lower FC between the left angular gyrus and right cerebellum, based on seed-to-voxel and inter-ROI analyses., Conclusion: Our results suggest that EDS in PD patients is associated with reduced spontaneous neural activity in the left angular gyrus and with reduced FC between the left angular gyrus and cerebellum. These findings may help understand and treat EDS in PD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg -1 and 0.167 mg·kg -1 , respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 μg·kg -1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)