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In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C 20 H 15 N 5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl 2 (C 20 H 15 N 5 )] n (pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl 2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC 50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC 50 value of 4.88 µM, outperforming both 2-DPHI and CdCl 2 . Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT-IR, 1 H NMR, 13 C NMR and UV-Vis spectroscopy.

Objective: The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients., Methods: One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models., Results: Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results., Conclusion: The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Petroleum-contaminated soil represents a significant environmental and public health challenge on a global scale. Microbial bioremediation has shown potential, yet the role of enzymes in enhancing petroleum degradation remains underexplored. In this study, the synergistic effects of Rhodococcus rhodochrous (R.rh) and Bacillus subtilis-derived laccase (BsLac) was investigated in the remediation of petroleum-contaminated soil. Immobilized R.rh (PSIMRH) and BsLac (ADIMLac) exhibited higher petroleum degradation rates than their free state, achieving 78.3% and 56.3% degradation in liquid systems, respectively. The combined treatment of PSIMRH and ADIMLac demonstrated a synergistic effect on petroleum degradation, achieving 43.6% with a maximum degradation constant of 0.0335 d -1 , representing a 202.7% improvement over untreated soil. PSIMRH enhanced petroleum degradation through microbial metabolism, while ADIMLac accelerated the initial breakdown of complex hydrocarbons into simpler, more bioavailable ones via enzymatic oxidation, providing growth substrates for microbes and significantly improving petroleum degradation rates. The microbial analysis revealed an increase abundance of known petroleum-degrading bacterial genera, including Rhodococcus, Lysobacter, Micromonospora, and Streptomyces. However, the presence of BsLac appeared to reduce the competitive advantage of Rhodococcus, promoting the proliferation of indigenous strains like Lysobacter and Streptomyces. These results suggest that enzyme-microbe synergy can enhance the bioremediation process by altering microbial community dynamics and accelerating petroleum degradation. This study attempts to remediate petroleum-contaminated pollution with the combined use of strains and enzymes, providing a new approach for the remediation of other pollution problems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tungsten-modified CeO 2 is an excellent catalyst for the catalytic conversion of ammonia. However, the geometric and electronic properties of this catalyst and the detailed reaction mechanisms are not well understood. In this work, the potential configurations of various monomer tungsten oxides supported on the CeO 2 (111) surface (WO X (x = 0-4)/CeO 2 (111)) are systematically studied and their relative stabilities are evaluated by using on-site Coulomb interaction corrected density functional theory calculations. Their performances are also investigated in enhancing the catalytic efficiency of NH 3 adsorption and activation. It is found that the WO x clusters can always form tetrahedron-like structures on the CeO 2 (111) surface, and the CeO 2 (111) can exhibit both oxygen- and electron-storage roles to help the WO X maintain such tetrahedron-like WO 4 structures and keep the W species at the highest 6+ state. Moreover, the flexibility of the tetrahedral WO 4 structure leads to the preferential heterolytic NH 3 dissociation at the WO sites, forming stable WNH 2 and OH species. This study deepens the understanding of the unique oxygen- and electron-storage effects of the CeO 2 support, it also provides valuable insights into the extraordinary catalytic properties of the W-modified CeO 2 in NH 3 conversion, paving the way for the rational design of more efficient CeO 2 -based NH 3 treatment catalysts., (© 2024 Wiley‐VCH GmbH.)

Cisplatin is a cornerstone chemotherapy for nasopharyngeal carcinoma (NPC); however, certain patients are ineligible for cisplatin-based regimens. This phase 2 trial (NCT04405622) evaluated the efficacy and safety of gemcitabine and toripalimab in previously untreated patients with recurrent or metastatic NPC who were either ineligible for cisplatin or had experienced severe adverse events from prior cisplatin-based treatments. Patients received gemcitabine (1,000 mg/m 2 ) and toripalimab (240 mg) every three weeks for six cycles, followed by toripalimab monotherapy for up to two years. The primary endpoint was the incidence of grade ≥3 adverse events, while secondary endpoints included objective response rate (ORR) and overall survival (OS). Of 30 screened patients, 21 were enrolled. No treatment-related fatalities occurred, with the most frequent adverse events being headache and nausea. The ORR was 61.9%, coupled with a disease control rate of 100%. Overall, gemcitabine plus toripalimab demonstrated low toxicity and promising efficacy for this specific patient cohort., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to examine the influence of the Neuregulin-1 (NRG1)/ERBB4 signaling pathway on the function of human pulmonary artery endothelial cells (HPAECs) and investigate the underlying mechanisms. Enzyme-linked immunosorbent assay indicated that ERBB4 levels in the serum of patients with pulmonary embolism (PE) were significantly higher than those of healthy controls ( p  < 0.05). In cellular studies, thrombin stimulation for 6 h led to a significant decrease in cell viability and overexpression of ERBB4 compared to control ( p  < 0.05). In the NRG1 group, apoptosis of HPAECs was reduced ( p  < 0.05), accompanied by a decrease in ERBB4 expression and an increase in p-ERBB4, phosphorylated serine/threonine kinase proteins (Akt) (p-Akt), and p-phosphoinositide 3-kinase (PI3K) expression ( p  < 0.05). In the AG1478 group, there was a significant increase in HPAEC apoptosis and a significant decrease in p-ERBB4 and ERBB4 expression compared to the Con group ( p  < 0.05). In the AG1478 + NRG1 group, there was an increase in the apoptosis rate and a significant decrease in the expression of p-ERBB4, ERBB4, p-Akt, and phosphorylated PI3K compared to the NRG1 group ( p  < 0.05). In animal studies, the PE group showed an increase in the expression of ERBB4 and p-ERBB4 compared to the Con group ( p  < 0.05). NRG1 treatment led to a significant reduction in embolism severity with decreased ERBB4 expression and increased p-ERBB4 expression ( p  < 0.05). Gene set enrichment analysis identified five pathways that were significantly associated with high ERBB4 expression, including CHOLESTEROL HOMEOSTASIS, OXIDATIVE PHOSPHORYLATION, and FATTY ACID METABOLISM ( p  < 0.05). Therefore, NRG1 inhibits apoptosis of HPAECs, accompanied by a decrease in ERBB4 and an increase in p-ERBB4. NRG1 inhibition in HPAECs apoptosis can be partially reversed by inhibiting ERBB4 expression with AG1478. ERBB4 has the potential to be a novel biological marker of PE., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu 2+ -DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu 2+ -DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H 2 O 2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu 2+ -DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events. Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).

ADP-ribosylation (ADPRylation), which encompasses poly(ADP-ribosyl)ation and mono(ADP-ribosyl)ation, is an important post-translational modification catalysed by the poly(ADP-ribose) polymerase (PARP) enzyme superfamily. The process involves writers (PARPs) and erasers (ADP-ribose hydrolases), which work together to precisely regulate diverse cellular and molecular responses. Although the PARP-mediated synthesis of ADP-ribose (ADPr) has been well studied, ADPr degradation by degrading enzymes deserves further investigation. Nonetheless, recent studies have provided important new insights into the biology and functions of ADPr hydrolases. Notably, research has illuminated the significance of the poly(ADP-ribose) degradation pathway and its activation by the coordinated actions of poly(ADP-ribose) glycohydrolase and other ADPr hydrolases, which have been identified as key components of ADPRylation signalling networks. The degradation pathway has been proposed to play crucial roles in key cellular processes, such as DNA damage repair, chromatin dynamics, transcriptional regulation and cell death. A deep understanding of these ADPr erasing enzymes provides insights into the biological roles of ADPRylation in human health and disease aetiology and paves the road for the development of novel therapeutic strategies. This review article provides a summary of current knowledge about the biochemical and molecular functions of ADPr erasers and their physiological implications in human pathology.

Rice false smut, caused by Ustilaginoidea virens , threatens rice production by reducing yields and contaminating grains with harmful ustiloxins. However, studies on resistance genes are scarce. In this study, the resistance level of IR28 (resistant cultivar) to U. virens was validated through artificial inoculation. Notably, a reactivation of resistance genes after transient down-regulation during the first 3 to 5 dpi was observed in IR28 compared to WX98 (susceptible cultivar). Cluster results of a principal component analysis and hierarchical cluster analysis of differentially expressed genes (DEGs) in the transcriptome exhibited longer expression patterns in the early infection phase of IR28, consistent with its sustained resistance response. Results of GO and KEGG enrichment analyses highlighted the suppression of immune pathways when the hyphae first invade stamen filaments at 5 dpi, but sustained up-regulated DEGs were linked to the 'Plant-pathogen interaction' (osa04626) pathway, notably disease-resistant protein RPM1 (K13457, CNLs, coil-coiled NLR). An analysis of CNLs identified 245 proteins containing Rx-CC and NB-ARC domains in the Oryza sativa Indica genome. Partial candidate CNLs were shown to exhibit up-regulation at both 1 and 5 dpi in IR28. This study provides insights into CNLs' responses to U. virens in IR28, potentially informing resistance mechanisms and genetic breeding targets.

Background: The relationship of hypoglycemic drugs, inflammatory proteins and gallbladder diseases remain unknown., Methods: Four hypoglycemic drugs were selected as exposure: glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin. The outcome were two gallbladder diseases: cholecystitis and cholelithiasis. Mendelian Randomization (MR) was employed to determine the association between hypoglycemic drugs and gallbladder diseases., Results: DPP-4i and SGLT-2i had no effect on cholecystitis and cholelithiasis. However, a causal relationship was found between inhibition of ETFDH gene, a target of metformin expressed in cultured fibroblasts, and cholelithiasis (OR: 0.84, 95 %CI: (0.72,0.97), p = 0.021), as well as between GLP1R expression in the brain caudate basal ganglia and cholecystitis (OR: 1.29, 95 %CI: (1.11,1.49), p = 0.001). The effect of ETFDH inhibition on cholelithiasis through Interleukin-10 receptor subunit beta (IL-10RB) levels and Neurotrophin-3 (NT-3) levels, with a mediated proportion of 8 % and 8 %, respectively., Conclusion: Metformin plays a protective role in cholelithiasis, while GLP-1RA have a harmful effect on the risk of cholecystitis. Metformin may reduce the risk of cholelithiasis by modulating the levels of Neurotrophin-3 (NT-3) and Interleukin-10 receptor subunit beta (IL-10RB). Further clinical and mechanistic studies are required to confirm these findings., 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.)

Aims: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies., Methods: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy., Results: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays., Conclusions: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC 50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 μM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner., 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 Inc. All rights reserved.)

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment., (© 2024 John Wiley & Sons Ltd.)

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs., (© 2024. The Author(s).)

Background: Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations., Aim: To illustrate the major areas of research and forward-looking directions over the past twenty-six years., Methods: Using the Web of Science Core Collection database, a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023. We used Citespace (Version 6.2.4) and Bibliometrix package (Version 4.3.0) to visualize the analysis of all publications including country, institutional affiliations, authors, and keywords., Results: In total, 346 articles were retrieved. Surgical Endoscopy had with the largest number of publications and was cited in this field. The United States was a core research country in this field. Yonsei University was the most productive institution. The current focus of this field is on rectal surgery, long-term prognosis, perioperative management, previous surgical experience, and the learning curve., Conclusion: The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997. This study provides new perspectives and ideas for future research in this field., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Asymmetric enamine alkylation represents a powerful tool for stereoselective C-C bond formation; in contrast, the development of enantioselective enamine acylation remains elusive. Here, we report that a chiral phosphoric acid can render an in-situ-formed enamine to undergo a stereoselective intramolecular α-carbon acylation, providing an alternative approach for the synthesis of useful pyrrolinones and indolinones bearing tetrasubstituted stereocenters. Utilizing an effective integration of the desymmetrization strategy and bifunctional organocatalysis, the first example of enantioselective enamine acylation is achieved by employing readily available aminomalonic esters and cyclic ketones. Instead of reactive and moisture-sensitive acyl chlorides, common esters with low electrophilicity were successfully used as efficient acylating reagents via hydrogen bonding interactions. The utility is demonstrated in the concise and enantioselective synthesis of (+)-LipidGreen I and II. Experimental studies and DFT calculations establish the reaction pathway and the origin of stereocontrol.

C-type lectin (CTL) plays a vital role in parasite adhesion, invading host's cells and immune escape. The objective of this research was to explore whether recombinant T. spiralis CTL (rTsCTL) binding with syndecan-1 damages intestine epithelial integrity and mediates T. spiralis intrusion in mice. The results showed that rTsCTL interacted with syndecan-1 and activated STAT3 pathway in gut epithelium, decreased tight junctions (TJs) expressions and damaged gut epithelium integrity, promoted T. spiralis intrusion, and increased expression level of inflammatory cytokine and mucin. The syndecan-1 inhibitor (β-xyloside) and STAT3 phosphorylation inhibitor (Stattic) significantly suppressed syndecan-1 expression and STAT3 pathway activation, reduced the expression levels of TJs, pro-inflammatory cytokines (TNF-α and IL-1β), Muc2 and Muc5ac, and declined intestinal permeability in T. spiralis-infected mice. These results revealed that the inhibitors suppressed T. spiralis invasion and development in gut mucosa, decreased intestinal adult burdens and relieved gut inflammation. These findings further testified that the in vivo binding of TsCTL with syndecan-1 destroyed enteral mucosal epithelial integrity and promoted T. spiralis intrusion of gut mucosa via activating STAT3 pathway and decreasing TJs expression. TsCTL could be deemed as a promising vaccine target to interrupt T. spiralis infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Fever is a common side effect following thermal ablation in patients with hepatocellular carcinoma (HCC), yet its impact on prognosis remains unclear., Materials and Methods: This retrospective study included initial HCC patients who underwent US-guided percutaneous microwave ablation at 13 hospitals between January 2006 and February 2021. All patients were categorized into afebrile, transient low-grade fever (TLF), and prolonged or high-grade fever (PHF) groups. Primary outcomes included very early recurrence (VER) and early recurrence (ER), secondary outcomes were disease-free survival (DFS) and overall survival (OS). Fever cut-offs for VER/ER were established using restrictive cubic splines and adjusted Cox model. Survival analyses used the Kaplan-Meier method., Results: A total of 1458 initial HCC patients (mean age, 59±11[SD]; 1146 men). Compared to afebrile individuals, patients with TLF (temperatures ranging 37.0-38.8°C for 1-2 d), showed independent protective effects against VER (HR, 0.73; 95% CI: 0.57,0.95; P=0.02) and ER (HR, 0.66; 95% CI: 0.54,0.81; P<0.001), however, PHF showed no differences in VER (HR, 0.99; 95% CI: 0.76,1.30; P=0.96) and ER (HR, 0.86; 95% CI: 0.69,1.07; P=0.17). With a median follow-up of 47 months (IQR:26-79), the median DFS for TLF patients was 40 months, superior to afebrile (30 mo, P=0.019) and PHF patients (33 mo, P=0.049). The 5-year OS rate for TLF patients was 73.2%, higher than afebrile (69.3%, P=0.02) and PHF patients (66.7%, P=0.03). No significant difference was found in DFS and OS between afebrile and PHF patients (P=0.90 and 0.71). Notably, TLF patients exhibited the highest lymphocyte counts increasing median 7 days after ablation (P<0.001 vs. afebrile and P=0.01 vs. PHF)., Conclusion: Transient low-grade fever following percutaneous microwave ablation in hepatocellular carcinoma patients demonstrated protection against early recurrence, possibly attributed to the short-term activation of lymphocytes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear., Objectives: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19., Design, Setting, Participants and Interventions: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days., Main Outcome Measures: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO 2 ) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO 2 and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO 2 , the duration of prone positioning, and adverse events were recorded as well., Results: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO 2 above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO 2 was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness., Conclusion: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO 2 and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; Epub ahead of print., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Two new species of Eupolyphaga ( E.bicolor Han, Che & Wang, sp. nov. and E.nigra Han, Che & Wang, sp. nov. ) and six new species of Pseudoeupolyphaga ( P.flava Han, Che & Wang, sp. nov. , P.deficiens Han, Che & Wang, sp. nov. , P.magna Han, Che & Wang, sp. nov. , P.longiseta Han, Che & Wang, sp. nov. , P.latizona Han, Che & Wang, sp. nov. , and P.baimaensis Han, Che & Wang, sp. nov. ) are described and illustrated. The female external genitalia and spermathecae of these two genera are reported and the role of these characters in species delimitation is discussed., Competing Interests: The authors have declared that no competing interests exist., (Wei Han, Yan-Li Che, Pei-Jun Zhang, Zong-Qing Wang.)

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants., (© 2024. The Author(s).)

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

This work systematically studied thermocatalytic and photocatalytic pathways of formaldehyde degradation and H-assisted O 2 reduction over a Pt 13 /anatase-TiO 2 (101) composite via DFT calculations together with constrained molecular dynamics (MD) simulations. We show that photocatalytic O 2 reduction on Pt/TiO 2 can directly generate • OH radicals (*O 2 → *OOH → • OH) via two hydrogenation steps with small barriers, and the product selectivity (*H 2 O 2 or • OH) is decided by the relative position between catalyst Fermi level and • OH/*H 2 O 2 redox potential (theoretical determination of 0.07 V referencing to the SHE). Such a novel reaction channel was furthermore validated at the liquid-solid interface via constrained MD simulations and experimental electron paramagnetic resonance detections, and a wide range of H resources, e.g., *HCHO, *HCO, *H (H + + e - ), can always drive the direct • OH generation. The additional portion of e - -triggered • OH radicals are prone to diffuse into solution or the TiO 2 surface and furthermore cooperate with the conventional h + -driven photooxidations.

Background: As a genus within the Clavicipitaceae, Metarhizium exhibits rich morphological and ecological diversity, with a wide distribution and a variety of hosts. Currently, sixty-eight species of Metarhizium have been described., New Information: A new species of Metarhizium , M.puerense (Hong Yu bis), was described in Pu'er City, Yunnan Province, south-western China. Based on morphological characteristics and multilocus phylogenetic analyses, Metarhiziumpuerense was confirmed to be phylogenetically related to M.album , but was clearly separated and formed a distinct branch. In contrast, the host of Metarhiziumalbum was plants and leafhoppers and that lepidopteran larvae were the host of M.puerense . The diagnostic features of M.puerense were solitary to multiple stromata and smooth-walled, cylindrical with rounded apices conidia., (Jin Mei Ma, Zhi Qin Wang, Zhi Li Yang, Yue Chen, Song Yu Li, Hong Yu.)

Objective: To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes. Methods: A total of 258 patients diagnosed EC undergoing surgery in Peking University People's Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative. Results: (1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences ( χ 2 =7.79, P =0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P <0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P <0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P <0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ 2 =12.15, P <0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ 2 =3.94, P =0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P >0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P <0.05). (4) Lymph node metastasis ( HR =6.93, 95% CI : 1.15-41.65; P =0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression ( HR =0.04, 95% CI : 0.01-0.14; P <0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions: LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease., 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.)

ZnO is an important catalytic material for CO/CO 2 hydrogenation. In this work, the pristine ZnO(101̄0) and the surfaces with Zn-O dimer vacancies (ZnO(101̄0)-(Zn-O) DiV ) and oxygen vacancies are calculated. We find that the hydride (H - ) species can be generated via heterolytic H 2 dissociation on these surfaces, and that ZnO(101̄0)-(Zn-O) DiV only needs to overcome the energy barrier of ∼0.10 eV. This is because the ZnO system has flexible orbitals for electron storage and release and the low-coordinated Zn 3c atoms at the defect sites can form stable Zn-H - covalent bonds with high symmetry. Flexible Zn orbitals also impart the unique feature of activating multiple electrophilic adsorbates simultaneously as excess electrons exist. Moreover, we show that the covalent Zn-H - species can regulate the catalytic activity and selectivity for CO 2 hydrogenation by preferentially producing *HCOO intermediates at Zn-O dimer vacancies. These results may help in the design of efficient Zn-based hydrogenation catalysts., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Background: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT., Methods: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety., Results: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676)., Conclusion: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors., Patients and Methods: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials., Results: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%., Conclusions: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

After Gulielmina was erected and Ophiotheca was resurrected based on some species originally included in Perichaena (Trichiaceae, Trichiales, Myxomyxetes), some specimens from the Herbarium of Fungi of Nanjing Normal University previously identified as Perichaena species were reexamined from morphological and two-gene (nuclear 18S rDNA and elongation factor-1 alpha) phylogenetic perspectives. In this study, two new myxomycete species, Gulielmina subreticulospora and Ophiotheca dictyospora, are described. Gulielmina subreticulospora shows the following character combination: branched plasmodiocarps, single peridium with circular protrusions in the inner surface, capillitium (2.4-)2.8-3.0(-3.4) μm in diameter, spores (7.4-)8.0-8.5(-9.0) μm in diameter and sub-reticulated. Ophiotheca dictyospora shows the following character combination: sessile sporocarps to short plasmodiocarps, single peridium with a densely irregular network and protrusions in the inner surface, capillitium (2.7-)3.5-5.0(-7.1) μm in diameter, uneven, decorated with spines of uneven size, spores (7.7-)8.2-8.6(-9.4) μm in diameter including obviously complete cristate reticulation with serrated edges, with deep and clear grids. Both new taxa were compared with related species and their genetic isolation was statistically tested. Moreover, a comprehensive morphological description and a detailed figure plate are provided for Perichaena verrucifera, and its phylogenetic position is determined., 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 GmbH. All rights reserved.)

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Microglia are innate immune cells in the brain and show exceptional heterogeneity. They are key players in brain physiological development regulating synaptic plasticity and shaping neuronal networks. In pathological disease states, microglia-induced synaptic pruning mediates synaptic loss and targeting microglia was proposed as a promising therapeutic strategy. However, the effect of microglia depletion and subsequent repopulation on dendritic spine density and neuronal function in the adult brain is largely unknown. In this study, we investigated whether pharmacological microglia depletion affects dendritic spine density after long-term permanent microglia depletion and after short-term microglia depletion with subsequent repopulation. Long-term microglia depletion using colony-stimulating-factor-1 receptor (CSF1-R) inhibitor PLX5622 resulted in increased overall spine density, especially of mushroom spines, and increased excitatory postsynaptic current amplitudes. Short-term PLX5622 treatment with subsequent repopulation of microglia had an opposite effect resulting in activated microglia with increased synaptic phagocytosis and consequently decreased spine density and reduced excitatory neurotransmission, while Barnes maze and elevated plus maze testing was unaffected. Moreover, RNA sequencing data of isolated repopulated microglia showed an activated and proinflammatory phenotype. Long-term microglia depletion might be a promising therapeutic strategy in neurological diseases with pathological microglial activation, synaptic pruning, and synapse loss. However, repopulation after depletion induces activated microglia and results in a decrease of dendritic spines possibly limiting the therapeutic application of microglia depletion. Instead, persistent modulation of pathological microglia activity might be beneficial in controlling synaptic damage., (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8 + T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer., (© 2024 Wiley‐VCH GmbH.)

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO 2 ) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO 2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO 2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis., 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 Inc. All rights reserved.)

Utilizing spin pumping, we present a comparative study of the spin-charge conversion in RuO&#95;{2}(101) and RuO&#95;{2}(110) films. RuO&#95;{2}(101) shows a robust in-plane crystal-axis dependence, whereas RuO&#95;{2}(110) exhibits an isotropic but stronger one. Symmetry-based analysis and first-principles calculations reveal that the spin-charge conversion in RuO&#95;{2}(110) originates from the inverse spin Hall effect (ISHE) due to nodal lines splitting. In RuO&#95;{2}(101), the ISHE also dominates although the inverse spin splitting effect (ISSE) may coexist. These findings, in sharp contrast to previously attributed ISSE, are further corroborated by the reciprocal relation between the spin pumping and the spin-torque ferromagnetic resonance measurements.

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N 3 C-N sites with asymmetric in-plane coordinated Fe-N 3 C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity ( E 1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N 4 -N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density ( P max ) of 130 mW/cm 2 , outperforming the commercial Pt/C catalyst (OCV = 1.42 V; P max = 119 mW/cm 2 ). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N 3 C-N structure shifted upward, which enhances its electron-donating ability, favors O 2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

Background: The aim of this study was to elucidate the histogenesis and genetic underpinnings of fibromatosis-like undifferentiated gastric carcinoma (FLUGC), a rare pathological entity., Method: Through a detailed analysis of seven cases, including histopathological evaluation, CTNNB1 gene mutation screening, human epidermal growth factor receptor 2 (HER2) protein level quantification, and HER2 gene amplification assessment to identify the pathological and molecular characteristics of FLUGC., Results: Of the seven patients in this study, five were male and two were female (age: 39-73 years). Four patients presented with lesions in the gastric antrum and three had lesions in the lateral curvature of the stomach. Histopathologically, over 90% of the tumor consisted of aggressive fibromatosis-like tissue, including proliferating spindle fibroblasts and myofibroblasts and varying amounts of collagenous fibrous tissues. Undifferentiated cancer cells, accounting for less than 10%, were dispersed among the aggressive fibromatosis-like tissues. These cells were characterized by their small size and were relatively sparse without glandular ducts or nested mass-like structures. Immunophenotyping results showed positive expression of CKpan, CDX2, villin, and p53 in undifferentiated cancer cells; positive expression of vimentin in aggressive fibromatosis-like tissue; positive cytoplasmic expression of β-catenin; and focal cytoplasmic positive expression of smooth muscle actin (SMA). Genetic analysis did not reveal any mutations in the CTNNB1 gene test, nor was there amplification in the HER2 gene fluorescence in situ hybridization (FISH) test. Additionally, the Epstein-Barr encoding region (EBER) of in situ hybridization was negative; and the mismatch repair (MMR) protein was positive. Programmed cell death-1 (PD-1) was < 1-5%; programmed cell death ligand 1 (PD-L1): TPS = 1-4%, CPS = 3-8., Conclusion: The study highlights the significance of CTNNB1, HER2, EBER, and MMR as pivotal genetic markers in FLUGC, underscoring their relevance for diagnosis and clinical management. The rarity and distinct pathological features of FLUGC emphasize the importance of accurate diagnosis to prevent underdiagnosis or misdiagnosis and to raise awareness within the medical community., (© 2024. The Author(s).)

Objective: The human microbiota plays a key role in cancer diagnosis, pathogenesis, and treatment. However, osteosarcoma-associated oral microbiota alterations have not yet been unraveled. The aim of this study was to explore the characteristics of oral microbiota in osteosarcoma patients compared to healthy controls, and to identify potential microbiota as a diagnostic tool for osteosarcoma., Methods: The oral microbiota was analyzed in osteosarcoma patients (n = 45) and matched healthy controls (n = 90) using 16S rRNA MiSeq sequencing technology., Results: The microbial richness and diversity of the tongue coat were increased in osteosarcoma patients as estimated by the abundance-based coverage estimator indices, the Chao, and observed operational taxonomy units (OTUs). Principal component analysis delineated that the oral microbial community was significant differences between osteosarcoma patients and healthy controls. 14 genera including Rothia, Halomonas, Rhodococcus, and Granulicatella were remarkably reduced, whereas Alloprevotella, Prevotella, Selenomonas, and Campylobacter were enriched in osteosarcoma. Eventually, the optimal four OTUs were identified to construct a microbial classifier by the random forest model via a fivefold cross-validation, which achieved an area under the curve of 99.44% in the training group (30 osteosarcoma patients versus 60 healthy controls) and 87.33% in the test group (15 osteosarcoma patients versus 30 healthy controls), respectively. Notably, oral microbial markers validated strong diagnostic potential distinguishing osteosarcoma patients from healthy controls., Conclusion: This study comprehensively characterizes the oral microbiota in osteosarcoma and reveals the potential efficacy of oral microbiota-targeted biomarkers as a noninvasive biological diagnostic tool for osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Wang, Zhang, Ren and Wang.)

Amphichorda has been previously accepted as a member of the Cordycipitaceae and currently it is considered a member of the Bionectriaceae. The substrates of Amphichorda were complex and varied, being mainly animal faeces. This study reports two new species of Amphichorda from Yunnan Province in south-western China. Based on the five-gene (nr SSU , nr LSU , tef-1α , rpb1 and rpb2 ) sequence and ITS data phylogenetic analysis, two new species, namely A.excrementa and A.kunmingensis , are proposed and a detailed description of the new species is provided. Amphichordaexcrementa and A.kunmingensis were isolated from animal faeces in the park. The morphological characteristics of two novel species and seven known species in Amphichorda are also compared., Competing Interests: The authors have declared that no competing interests exist., (Zhi-Qin Wang, Jing Zhao, Quan-Ying Dong, Yao Wang, Ying-Ling Lu, Run Luo, Hong Yu.)

Purpose: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment., Methods and Materials: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS)., Results: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06)., Conclusions: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Stomatal movement is critical for water transpiration, gas exchange, and responses to biotic stresses. Abscisic acid (ABA) induces stomatal closure to prevent water loss during drought. We report that Arabidopsis CIPK8 negatively regulates ABA-mediated stomatal closure and drought tolerance. CIPK8 is highly enriched in guard cells and transcriptionally induced by ABA. Functional loss of CIPK8 results in hypersensitive stomatal closure to ABA and enhanced drought tolerance. Guard cell-specific downregulation of CIPK8 mimics the phenotype of cipk8 whereas guard cell-specific expression of a constitutive active CIPK8 (CIPK8 CA ) has an opposite effect, suggesting a cell autonomous activity of CIPK8. CIPK8 physically interacts with CBL1 and CBL9. Functional loss of CBL1 and CBL9 mimics ABA-hypersensitive stomatal closure of cipk8 whereas abolishes the effect of CIPK8 CA , indicating that CIPK8 and CBL1/CBL9 form a genetic module in ABA-responsive stomatal movement. SlCIPK7, the functional homolog of CIPK8 in tomato (Solanum lycopersicum), plays a similar role in ABA-responsive stomatal movement. Genomic editing of SlCIPK7 results in more drought-tolerant tomato, making it a good candidate for germplasm improvement., (© 2024 John Wiley & Sons Ltd.)

The efficient synthesis of chiral 2,2-disubstituted indolin-3-ones is of great importance due to its significant synthetic and biological applications. However, catalytic enantioselective methods for de novo synthesis of such heterocycles remain scarce. Herein, a novel cyclizative rearrangement of readily available anilines and vicinal diketones for the one-step construction of enantioenriched 2,2-disubstituted indolin-3-ones is presented. The reaction proceeds through a self-sorted [3+2] heteroannulation/regioselective dehydration/1,2-ester shift process. Only chiral phosphoric acid is employed to promote the entire sequence and simplify the manipulation of this protocol. Various common aniline derivatives are successfully applied to asymmetric synthesis as 1,3-binuclephiles for the first time. Remarkably, the observed stereoselectivity is proposed to originate from an amine-directed regio- and enantioselective ortho-Csp 2 -H addition of the anilines to the ketones. A range of synthetic transformations of the resulting products are demonstrated as well., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Solid pseudopapillary neoplasms of the pancreas (SPN) share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes (PDAC with cystic changes), which may result in unnecessary surgery., Aim: To investigate the value of computed tomography (CT) in differentiation of SPN from PDAC with cystic changes., Methods: This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes, confirmed through pathological diagnosis. Quantitative and qualitative analysis was performed, including assessment of age, sex, tumor size, shape, margin, density, enhancement pattern, CT values of tumors, CT contrast enhancement ratios, "floating cloud sign," calcification, main pancreatic duct dilatation, pancreatic atrophy, and peripancreatic invasion or distal metastasis. Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes, and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination., Results: When compared to PDAC with cystic changes, SPN had a lower age (32 years vs 64 years, P < 0.05) and a slightly larger size (5.41 cm vs 3.90 cm, P < 0.05). SPN had a higher frequency of "floating cloud sign" and peripancreatic invasion or distal metastasis than PDAC with cystic changes (both P < 0.05). No significant difference was found with respect to sex, tumor location, shape, margin, density, main pancreatic duct dilatation, calcification, pancreatic atrophy, enhancement pattern, CT values of tumors, or CT contrast enhancement ratios between the two groups (all P > 0.05). The area under the receiver operating characteristic curve of the combination was 0.833 (95% confidence interval: 0.708-0.957) with 78.6% sensitivity, 81.3% specificity, and 80.4% accuracy in differentiation of SPN from PDAC with cystic changes., Conclusion: A larger tumor size, "floating cloud sign," and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem., Methods: This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score., Discussion: Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function., Trial Registration: Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 ., (© 2024. The Author(s).)