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Abstract This prospective, nonrandomized, open-label phase 2 trial (Chinese Clinical Trial Registry, ChiCTR2200061906) aimed to evaluate the effectiveness of adding the PD-1 antibody tislelizumab to perioperative chemotherapy in patients with locally advanced gastroesophageal junction adenocarcinoma (GEJA). This study enrolled patients with GEJA clinically staged as cT3-4aNanyM0 or cT1-2N+M0 from October 2022 to June 2023. Eligible patients were administered three preoperative and five postoperative 3-week cycles of treatment with PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. Thirty-two patients were enrolled. The median age was 60 years (range: 28–74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 93.8% (30/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. The R0 resection rate was 96.9% (31/32). MPR, pathological complete response (pCR) of primary tumors and ypT0N0 rates were 50.0% (16/32, 95% CI: 31.9–68.1%), 28.1% (9/32, 95% CI: 13.7–46.7%) and 25.0% (8/32, 95% CI: 11.5–43.4%), respectively. The surgical morbidity rate was 15.6% (5/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment periods, the rate of treatment-related grade 3–4 adverse events was 31.2% (10/32). At the date of 7th Jan 2025, 8 (25.0%) patients occurred recurrence. Therefore, perioperative tislelizumab plus chemotherapy demonstrated significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJA.

Abstract Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) are diverse in clinical presentation and are caused by complex and multiple factors, including genetic mutations and environmental factors. Numerous therapeutic approaches have been developed based on the genetic causes and potential mechanisms of ALS and HD. Currently, available treatments for various neurodegenerative diseases can alleviate symptoms but do not provide a definitive cure. Gene therapy, which aims to modify or express specific proteins for neuroprotection or correction, is considered a powerful tool in managing neurodegenerative conditions. To date, antisense oligonucleotide (ASO) drugs targeting the pathological genes associated with ALS and HD have shown promising results in numerous animal studies and several clinical trials. This review provides a comprehensive overview of the development, mechanisms of action, limitations, and clinical applications of ASO drugs in neurodegenerative diseases, with a specific focus on ALS and HD therapeutic strategies.

Abstract Background HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention. Methods The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA. This therapeutic effect was substantiated in various models: HEK 293 T cell, the HD 140Q-KI mouse, and the HD-KI pig model. The efficiency of the knockdown was analyzed through Western blot and RT-qPCR. Additionally, neuropathological changes were examined using Western blot, immunostaining, and RNA sequencing. The impact on motor abilities was assessed via behavioral experiments, providing a comprehensive evaluation of the treatment's effectiveness. Results CRISPR/CasRx system can significantly reduce HTT mRNA levels across various models, including HEK 293 T cells, HD 140Q-KI mice at various disease stages, and HD-KI pigs, and resulted in decreased expression of mHTT. Utilizing the CRISPR/CasRx system to knock down HTT RNA has shown to ameliorate gliosis in HD 140Q-KI mice and delay neurodegeneration in HD pigs. Conclusions These findings highlight the effectiveness of the RNA-targeting CRISPR/CasRx as a potential therapeutic strategy for HD. Furthermore, the success of this approach provides valuable insights and novel avenues for the treatment of other genetic disorders caused by gene mutations.

PirB is the main virulence factor of acute hepatopancreatic necrosis disease (AHPND) which induced the sloughing of hepatopancreatic cells and shrimp death. In addition, Litopenaeus vannamei aminopeptidase N (Lv-APN) is reported to be a functional receptor that mediates the pathogenicity by VpAHPND. This study aims to screen the PirB binding peptide to rescue the survival rate under VpAHPND infection. Here, the PirB toxin-binding peptides were selected using the random phage peptide library kit, and their biological function was verified by injecting them under VpAHPND challenge. The receptor candidates for PirB were genome-wide identified and selected based on gene expression profiles, and the biological function of Lv-APN1 was confirmed through RNAi. Docking analysis of Peptide-Lv-APN1 and PirB-Lv-APN1 was conducted using the MDockPeP server, with comparative analysis implied. As a result, a total of 11 PirB binding peptides were screened, among which P2 was found to effectively improve the shrimp survival rate under VpAHPND challenge. And knocked down of Lv-APN1, candidate receptor for PirB toxin, rescued mortality under VpAHPND challenge. Furthermore, docking analysis revealed that the interface of Lv-APN1 to rPirB was consistent with the P2 to rPirB, suggesting that P2 is likely to bind to PirB to block its binding to Lv-APN1 to reduce the mortality. In conclusion, both the injection of P2 and inference of Lv-APN1 can rescue the mortality of shrimp under VpAHPND challenge, and docking analysis revealed P2 is likely to bind to rPirB, blocking its binding to Lv-APN1 and reducing VpAHPND infection.

Semi-clathrate hydrates, with high latent heat, tunability, and excellent stability, show promise as phase change cold storage materials. To meet the varying phase change temperature requirements for different applications, this study investigated the dissociation behavior of hydrates formed from two tetrabutylammonium (TBA+) salt mixtures—FBS (TBAF, TBAB, TBAHSO4) and FCS (TBAF, TBAC, TBAHSO4)—at varying concentrations and ratios using differential scanning calorimetry. The results revealed that tuning the ratios of these mixtures enabled single-peak phase change regulation, ranging from 3.8 °C to 15.1 °C and 26 °C to 28.1 °C. The mixed tetrabutylammonium salt solutions exhibited a synergistic effect, enhancing phase change enthalpy beyond pure solutions, with peak values of 225.77 kJ/kg (FBS 0.7-0.3-0) and 239.48 kJ/kg (FCS 0.5-0.5-0). Further analysis indicated that reducing the molar mass of the mixed anions increased both phase change temperature and enthalpy, with FCS exhibiting a more pronounced improvement. For single-peak phase changes, maximum enthalpies of 225.77 kJ/kg (FBS) and 226.48 kJ/kg (FCS) were observed when the mixed anion molar masses were 25.69 and 20.96 kg/kmol, respectively. These finding highlight the potential of mixed tetrabutylammonium slat hydrates for applications, including high-energy density cold storage, multi-temperature range preservation, and advanced air conditioning systems.

Global warming alters freeze–thaw process frequency and intensity, impacting soil carbon cycles. Four soils from a 12-year straw return experiment were used: S0 (no straw), S1 (low rate of addition), S2 (medium rate), and S3 (high rate). Ten treatments with or without temporary straw addition at different rates were conducted to explore their effects on soil microbial biomass carbon (MBC) and dissolved organic carbon (DOC) under laboratory and field freeze–thaw conditions. Compared to constant temperature, the freeze–thaw process under laboratory conditions reduced MBC (5.79%~29.9%), whereas this trend was mitigated or reversed under field conditions. The alleviating effect of straw addition on the decrease in MBC was greater in S0 than in S1, S2, and S3 by an average of 31.7%. Medium rate straw application (S2 8 t/ha) provided appropriate labile C levels, enhancing microbial activity while keeping DOC low and reducing C loss risk. The results revealed discrepancies in freeze–thaw effects on soil labile OC between laboratory and field conditions, the mitigation of freeze–thaw impacts on MBC by straw addition, and the appropriate straw return rate in Liaohe Plain. Therefore, proper nutrient management can maintain and regulate microbial activity and soil labile C in areas with freeze–thaw cycles.

The mitochondrial genome of Rhinogobius wuyiensis Li & Zhong, 2007 was initially assembled using sequencing data from the Illumina HiSeq platform (San Diego, CA), resulting in a circular mitogenome of 16,502 base pairs with a pronounced A + T nucleotide bias. Maximum-likelihood (ML) and Bayesian inference (BI) revealed the phylogenetic relationships within the genus Rhinogobius, indicating that R. wuyiensis is closely related to a clade comprising R. maculagenys, R. shennongensis, R. niger, and R. lentiginis. This study enriches genetic resources and advances the understanding of phylogenetics within the genus Rhinogobius. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are diverse in clinical presentation and are caused by complex and multiple factors, including genetic mutations and environmental factors. Numerous therapeutic approaches have been developed based on the genetic causes and potential mechanisms of ALS and HD. Currently, available treatments for various neurodegenerative diseases can alleviate symptoms but do not provide a definitive cure. Gene therapy, which aims to modify or express specific proteins for neuroprotection or correction, is considered a powerful tool in managing neurodegenerative conditions. To date, antisense oligonucleotide (ASO) drugs targeting the pathological genes associated with ALS and HD have shown promising results in numerous animal studies and several clinical trials. This review provides a comprehensive overview of the development, mechanisms of action, limitations, and clinical applications of ASO drugs in neurodegenerative diseases, with a specific focus on ALS and HD therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention. Methods: The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA. This therapeutic effect was substantiated in various models: HEK 293 T cell, the HD 140Q-KI mouse, and the HD-KI pig model. The efficiency of the knockdown was analyzed through Western blot and RT-qPCR. Additionally, neuropathological changes were examined using Western blot, immunostaining, and RNA sequencing. The impact on motor abilities was assessed via behavioral experiments, providing a comprehensive evaluation of the treatment's effectiveness. Results: CRISPR/CasRx system can significantly reduce HTT mRNA levels across various models, including HEK 293 T cells, HD 140Q-KI mice at various disease stages, and HD-KI pigs, and resulted in decreased expression of mHTT. Utilizing the CRISPR/CasRx system to knock down HTT RNA has shown to ameliorate gliosis in HD 140Q-KI mice and delay neurodegeneration in HD pigs. Conclusions: These findings highlight the effectiveness of the RNA-targeting CRISPR/CasRx as a potential therapeutic strategy for HD. Furthermore, the success of this approach provides valuable insights and novel avenues for the treatment of other genetic disorders caused by gene mutations. [ABSTRACT FROM AUTHOR]

Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. While current studies have primarily focused on gene regulation mediated by full-length nuclear TDP-43, the potential effects of cytoplasmic TDP-43 fragments remain less explored. Our previous findings demonstrated that primate-specific cleavage of TDP-43 contributes to its cytoplasmic localization, prompting further investigation into its pathological effects. In the cynomolgus monkey brain, we observed that mutant or truncated TDP-43 was transported onto the ribosome organelle. Ribosome-associated transcriptomic analysis revealed dysregulation of apoptosis- and lysosome-related genes, indicating that cytoplasmic TDP-43 induces neurotoxicity by binding to ribosomes and disrupting mRNA expression. These findings provide mechanistic insights into the gain-of-function effects of pathological TDP-43.

Kinetic release of trace metals from soil dissolved organic matter (DOM) to solution is the key process controlling the mobility and bioavailability of trace metals in soil environment. However, due to the complexity of soil DOM, predicting the reaction rates of trace metals with soil DOM from different sources remains challenging. In this study, we developed a novel hybrid model integrating machine learning with mechanistic kinetics model, which can quantitatively predict the release rates of Cu and Cd from diverse soil DOM based on their compositions and properties. Our model quantitatively demonstrated that the molecular compositions of DOM controlled metal release rates, which had more profound impact on Cu than Cd. Our modeling results also identified two key factors affecting metal release rates, in which high concentrations of Ca and Mg ions in DOM significantly decreased the release rates of Cu and Cd, and the reassociation reactions of metal ions with DOM became more significant with the release of metals from DOM. This work has provided a unified kinetic modeling framework combining both mechanistic and data-driven approaches, which offers a new perspective for developing predictive kinetics models and can be applied to different metals and DOM in dynamic environments.

This study investigated the effects of fine-sized pork bone biochar particles on remediating As-contaminated soil and alleviating associated phytotoxicity to rice in 50-day short-term and 120-day full-life-cycle pot experiments. The addition of micro-nanostructured pork bone biochar (BC) pyrolyzed at 400 and 600 °C (BC400 and BC600) significantly increased the As-treated shoot and root fresh weight by 24.4-77.6%, while simultaneously reducing tissue As accumulation by 26.7-64.1% and increasing soil As content by 17.1-27.1% as compared to As treatment. Microbial community analysis demonstrated that BC600 and BC400 treatments increased the proportion of plant growth-promoting microbes such as Ceratobasidium and Achromobacter by 33-81.6% in the roots and As adsorption-associated Bacillus by 1.15-1.59-fold in the rhizosphere soil. Metabolomic profiling suggests that BC and As coexposure triggered differentially expressed metabolites (DEMs) enriched in lipid, carbohydrate, and amino acid metabolic pathways, all of which could alleviate As-induced phytotoxicity and promote plant As tolerance. Importantly, the quality of As-treated rice grains was improved by the BC amendments. This study demonstrates the significant potential of BC for enhancing crop growth and minimizing the As-induced phytotoxicity to rice and provides a framework for a promising strategy for remediating heavy metal(loid)-contaminated soil while simultaneously promoting food safety.

The mitochondrial genome of Rhinogobius wuyiensis Li & Zhong, 2007 was initially assembled using sequencing data from the Illumina HiSeq platform (San Diego, CA), resulting in a circular mitogenome of 16,502 base pairs with a pronounced A + T nucleotide bias. Maximum-likelihood (ML) and Bayesian inference (BI) revealed the phylogenetic relationships within the genus Rhinogobius , indicating that R. wuyiensis is closely related to a clade comprising R. maculagenys , R. shennongensis , R. niger , and R. lentiginis . This study enriches genetic resources and advances the understanding of phylogenetics within the genus Rhinogobius ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Human immunodeficiency virus (HIV), a retrovirus of the Lentivirus genus, targets CD4 + T cells, causing immune dysfunction and AIDS. Approximately 8% of the human genome consists of human endogenous retroviruses (HERVs), ancient retroviral remnants that may interact with HIV. Despite antiretroviral therapy, challenges such as drug resistance, poor immune reconstitution (PIR), and reservoirs remain. This GEM discusses the impact of HIV on HERVs, the potential roles of HERVs in PIR and reservoirs, and provides insights into future research directions.

Background: Preoperative neoadjuvant chemoradiotherapy (nCRT) is considered to be the standard treatment strategy for locally advanced rectal cancer (LARC); however, the risk of adverse events and postoperative recurrence remains significant. This study aimed to evaluate the non-inferiority of neoadjuvant chemotherapy (nCT) compared with nCRT in patients with LARC and to assess the possibility of eliminating radiotherapy on the basis of guaranteed efficacy., Materials and Methods: We searched the PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing the efficacy of nCRT and nCT for LARC. The study protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO)., Results: A total of 2706 patients from 7 studies were included in the meta-analysis. There was no significant difference in overall survival (OS) or disease-free survival (DFS) between the nCT and nCRT groups. This study demonstrated a lower rate of infection (OR = 0.53, 95% CI = 0.34-0.82; P = 0.005), anastomotic leak (OR = 0.55, 95% CI = 0.34-0.87; P = 0.01), tumor regression grade (TRG) 0-1 (OR = 0.50, 95% CI = 0.36-0.69; P < 0.0001), preventive diverting ileostomy (OR = 0.41, 95% CI = 0.17-1.02; P = 0.05) and leukopenia (OR = 0.50, 95% CI = 0.25-1.01; P = 0.05) in the nCT group. However, there was no significant difference in the other toxic events, such as intestinal obstruction, urinary complications, diarrhoea, and surgical or pathological outcomes, such as clinical fistula, sphincter preservation, postoperative mortality (≤ 60 d), R0 resection, ypStage 0-I, positive circumferential resection margin (CRM +) or pathological complete response (pCR) between the two groups., Conclusion: This study indicated that OS and DFS were not lower in the nCT group than in the nCRT group. In addition, the nCT group had fewer complications. Preoperative nCT is expected to become a standard treatment option for most patients with stage II-III LARC. It is worth noting that radiotherapy can not be ignored for some patients who need to ensure the conversion effect of neoadjuvant therapy and strongly request to preserve organ function., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Eighteen cyclopenta[ b ]benzopyran derivatives ( 1 - 5 and 11 - 23 ) and 10 limonoids ( 6 - 10 and 24 - 28 ) were identified from Aglaia edulis , including 10 undescribed compounds ( 1 - 10 ), all of which were identified by analysis of spectroscopic data, electronic circular dichroism calculations, and X-ray crystallography studies. Nine compounds displayed significant cytotoxic activity against three cancer cells, with IC 50 values of 3-900 nM. Sixteen compounds demonstrated potent antiviral activity on the dengue virus, with selectivity index values between 13.0 and 532.6. A mechanism of action investigation revealed that compound 11 may function as an eIF4E activator, which could suppress the expression of the E protein, thereby conferring significant activity against the dengue virus.

Two new withanolide derivatives (1 and 2) and 12 known withanolide analogs (3-14) were identified from the aerial part of Physalis angulata var. villosa Bonati. Their structures were determined by various spectral data, quantum chemical calculations, and sugar derivatization methods. Three compounds (2, 3, and 14) demonstrated good nitric oxide inhibitory effects against lipopolysaccharide-stimulated RAW264.7 cells, with IC 50 values of 4.93 ± 0.22-8.58 ± 0.83 µM. The present study suggests that withanolide derivatives have potential anti-inflammatory activity and could be used to treat inflammation-related diseases. Moreover, the chemotaxonomic implications of the isolates are further investigated., (© 2025 Wiley‐VHCA AG, Zurich, Switzerland.)

Three novel quinoline alkaloids, tetradiunitiside A (1), tetradiunitiside B (2), and glycohaplopine-6-O-α-l-rhamnopyranoside (3), along with eight known ones (4-11), were isolated from the fruits of Tetradium glabrifolium. Their structures were inferred by IR, 1D NMR and 2D NMR, and HR-ESI-MS spectra. All the isolated compounds were evaluated for their antibacterial activities. Compounds 1-11 had potential antibacterial activities against Bacillus gasoformans, Bacillus subtilis, Pseudomonas solanacearum, and Pseudomonas aeruginosa, with minimum inhibitory concentration (MIC) values ranging from 100 to 3.125 µg/mL. Among them, compound 6 showed the most significant antibacterial activity against four strains of bacteria. These findings elucidated the pharmacological substance basis for the antibacterial activity of T. glabrifolium to some extent., (© 2025 Wiley‐VHCA AG, Zurich, Switzerland.)