It is difficult to treat malignant tumors, neurodegenerative diseases, and vascular diseases. For pathogenesis complexity of these diseases, researchers have focused on finding more drugs with high efficacy and low side effects. As a potential first-in-class drug, RRx−001 is expected to be an important first-line drug in tumor immunology, radiosensitizer and radio protecter. Currently, RRx−001 entered phase Ⅲ clinical trials. The data of the phase Ⅱ clinical trials demonstrated its safety and effectivity as a single agent and in combination with first-line clinical drugs. The novel mechanisms of RRx−001 and the result of main clinical trials were summarized, which could be valuable to further optimization and clinical application.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

Background: Adolescence is a critical period for physical, psychological, and social development. However, traditional school bullying and cyberbullying have emerged as major public health issues adversely affecting adolescent mental health. Aim: To estimate the prevalence of school bullying and cyberbullying among Mongolian adolescents, evaluate their impacts on psychosocial difficulties, self-harm, and suicidal ideation, and identify protective factors. Materials and Methods: A cross-sectional study was conducted under the international Global Child and Adolescent Mental Health Study (GCAMHS) framework. A randomized sample of 2936 adolescents aged 11–17 years was recruited from public schools across Ulaanbaatar, provincial, and rural areas. Psychosocial difficulties were assessed using the Strengths and Difficulties Questionnaire (SDQ). Statistical analyses included Chi-square tests, independent t-tests, and multivariable logistic regression modeling to compute adjusted odds ratios (aOR). Results: Overall, 24.2% (n=710) of adolescents reported school bullying victimization, while 15.4% experienced cyberbullying victimization. Boys experienced higher rates of traditional school victimization than girls (28.5% vs. 20.4%, p < 0.001), whereas girls were significantly more vulnerable to cyberbullying victimization (17.4% vs. 13.1%, p=0.001). Bullied students showed significantly higher total SDQ difficulty scores compared to non-victims (18.08±6.15 vs. 10.86±5.20, p < 0.001). Multivariable logistic regression analysis revealed that cyberbullying victimization was the strongest predictor for suicidal ideation (aOR=3.62, 95% CI: 2.79–4.69) and self-harm behavior (aOR=3.08, 95% CI: 2.41–3.93). School bullying victimization also increased suicidal ideation (aOR=2.79), while school safety perception served as an independent protective factor against suicidal ideation (aOR=0.64, 95% CI: 0.53–0.76). Conclusion Traditional and cyberbullying remain prevalent among Mongolian adolescents, with cyberbullying exerting a particularly strong negative impact on psychosocial distress, self-harm, and suicidal ideation. Enhancing school safety and implementing targeted psychosocial and digital safety interventions tailored to gender-specific needs are essential.

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Polysaccharides, a class of complex macromolecules, are distinguished by their diverse biological functions and essential role in functional foods. The distinctive biological activities of polysaccharides from medicine and food homology materials (MFPs), including immunomodulation, carbohydrate metabolism regulation, and lipid metabolism regulation properties, have attracted considerable scientific attention. The relationship between polysaccharides and gut microbiota is fundamental to human health, as polysaccharides demonstrate efficacy in ameliorating various conditions-from inflammatory bowel disease (IBD) to obesity and diabetes-through their influence on intestinal flora composition and diversity. Although polysaccharide research and applications show promise, significant challenges persist, particularly regarding extraction and purification methodologies, and the complete understanding of their biological mechanisms. Future investigations should prioritize understanding the correlation between polysaccharide structure and function, advancing large-scale production and application technologies, and establishing productive interdisciplinary collaborations. MFPs demonstrate significant potential for advancing sustainable development and human health, building upon current research findings. This paper presents a comprehensive review of global developments in the extraction, purification, structural characterization, biological activities, and applications of MFPs, emphasizing opportunities for scientific and technological innovations in specialized dietary food development.
Polysaccharides/isolation & purification* ; Humans ; Functional Food/analysis* ; Gastrointestinal Microbiome/drug effects* ; Animals

Objective: To investigate the feasibility and safety of modified interposed jejunal anastomosis following total laparoscopic proximal gastrectomy. Methods: The modification in the digestive tract reconstruction involves transecting the small intestine 2-3 cm below the gastrojejunostomy site and relocating the enteroenterostomy cranially, based on the double-tract anastomosis technique. Specifically, the jejunum and its mesenteric vessels are transected 20-25 cm from the ligament of Treitz. An overlap anastomosis is performed between the esophagus and the distal jejunum, with the common opening closed using a 15 cm barbed suture in a buried manner. A side-to-side gastrojejunostomy is completed under natural anatomical alignment, and the common opening is closed similarly. A side-to-side anastomosis is then created between the small intestine approximately 10 cm below the gastrojejunal anastomosis and the small intestine distal to the ligament of Treitz. Finally, the small intestine is transected 2-3 cm below the gastrojejunal anastomosis without dividing the mesenteric vessels. Results: From April to December 2024, a total of five patients with adenocarcinoma of the esophagogastric junction underwent modified interposed jejunum anastomosis following totally laparoscopic proximal gastrectomy at the Affiliated Tumor Hospital of Xinjiang Medical University. The median age of the group was 56 (53-74) years, including four males and one female, with a median body mass index of 24 (21-29) kg/m². Three cases were classified as Siewert type II and two as type III. All five patients successfully completed the totally laparoscopic proximal gastrectomy with modified interposed jejunum anastomosis. The median operative time was 215 (165-240) minutes, the digestive tract reconstruction time was 75 (65-93) minutes, and the intraoperative blood loss was 50 (30-100) ml. The median time to postoperative flatus was 71 (68-88) hours, with no severe complications occurring in any case. The median postoperative hospital stay was 8 (8-9) days. Within three months after surgery, none of the patients reported reflux symptoms such as acid regurgitation or heartburn. Conclusions: Total laparoscopic modified interposed jejunal anastomosis is safe and feasible, with relatively simple operative steps. It effectively prevents reflux while ensuring the passage of food through the remnant stomach and duodenal loop.
Humans ; Gastrectomy/methods* ; Jejunum/surgery* ; Laparoscopy/methods* ; Anastomosis, Surgical/methods* ; Male ; Female ; Middle Aged ; Aged ; Stomach Neoplasms/surgery* ; Plastic Surgery Procedures/methods*

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured