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Piwi-interacting RNAs (piRNAs) are predominantly expressed in germ cells and function in gametogenesis in various species. However, Piwi -deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear to be widely representative of mammals. Thus, the function of piRNAs in mammalian oogenesis remains largely unclear. Here, we generated Piwil1 - and Mov10l1 -deficient golden hamsters and found that all female and male mutants were sterile, with severe defects in embryogenesis and spermatogenesis, respectively. In Piwil1 -deficient female hamsters, the oocytes and embryos displayed aberrant transposon accumulation and extensive transcriptomic dysregulation, and the embryos were arrested at the two-cell stage with impaired zygotic genome activation. Moreover, PIWIL1-piRNAs exert a non-redundant function in silencing endogenous retroviruses in the oocytes and embryos. Together, our findings demonstrate that piRNAs are indispensable for generating functional germ cells in golden hamsters and show the value of this model species for piRNA studies in gametogenesis, especially those related to female infertility. A set of three papers reports that the piRNA pathway is essential for mammalian female fertility based on genetic perturbation experiments performed in golden hamsters.

The piRNA pathway is essential for female fertility in golden hamsters and likely humans, but not in mice. However, the role of individual PIWIs in mammalian reproduction remains poorly understood outside of mice. Here, we describe the expression profiles, subcellular localization, and knockout-associated reproductive defects for all four PIWIs in golden hamsters. In female golden hamsters, PIWIL1 and PIWIL3 are highly expressed throughout oogenesis and early embryogenesis, while knockout of PIWIL1 leads to sterility, and PIWIL3 deficiency results in subfertility with lagging zygotic development. PIWIL1 can partially compensate for TE silencing in PIWIL3 knockout females, but not vice versa. PIWIL1 and PIWIL4 are the predominant PIWIs expressed in adult and postnatal testes, respectively, while PIWIL2 is present at both stages. Loss of any PIWI expressed in testes leads to sterility and severe but distinct spermatogenesis disorders. These findings illustrate the non-redundant regulatory functions of PIWI-piRNAs in gametogenesis and early embryogenesis in golden hamsters, facilitating study of their role in human fertility. The role of PIWI proteins in mammalian reproduction remains poorly understood. Here, using golden hamsters, the authors establish expression profiles for all four PIWIs during gametogenesis and characterize their associated reproductive defects.

Background As medical education evolves from traditional knowledge dissemination to evidence-based practice, problem-solving, and lifelong learning, developing research literacy among students has become essential. This study investigates medical undergraduates’ research participation, challenges encountered, and attitudes toward research, aiming to inform curricular reforms that foster research-competent healthcare professionals. Methods A cross-sectional study was conducted using stratified random sampling to recruit full-time undergraduates across majors and academic years at Guangzhou Medical University (GMU). A validated self-administered questionnaire assessing extracurricular research engagement was distributed, yielding 410 valid responses. Data were analyzed using SPSS 25.0, with descriptive statistics and correlation tests applied. Results Students predominantly identified mentors through proactive engagement (55.1%) and faculty referral (42.4%), yet mentoring was infrequent, with only 35.6% receiving guidance biweekly. Significant discrepancies were reported between expected and actual guidance in topic selection, study design and data analysis. While 80.7% expressed satisfaction with institutional research training systems, demand for practical courses, particularly academic writing (64.4%) and clinical case discussions (58.8%), remained high. Self-evaluation indicated post-training improvements in statistical analysis and writing skills. Ranking of laboratory abilities showed strengths in experimental design and operational skills, with lower scores in aseptic techniques and normative laboratory habits. Conclusions Students' positive attitudes toward research reflect the effectiveness of recent educational reforms. However, disparities in participation linked to academic progression and program structure highlight systemic inequities in resource allocation. To address these gaps, we recommend prioritizing mentor training, enhancing time management, expanding funding opportunities, and fostering interdisciplinary collaboration. Implementing structured mentor-student pairing systems may further enhance equitable access to research experiences.

Nerve agents (NAs), a class of highly toxic organophosphorus (OP) compounds, pose a significant threat to global security. The development of integrated protective materials that can simultaneously capture airborne OPs, detect, and degrade them remains a formidable challenge. Inspired by lipase's specific binding to OPs, a biomimetic hydrogen‐bonded organic framework (HOF) is developed, FDU‐HOF‐5. It achieves highly efficient and selective adsorption of a sarin simulant, diethyl chlorophosphate (DCP), by combining size exclusion with molecular recognition via specific N─P bond formation, effectively distinguishing DCP from various OP analogues. Upon adsorption, the material responds within 5 s, enabling bimodal identification via a visual color change (yellow to red) and a fluorescence signal (99.7% quenching, 75 nm redshift). The adsorbed DCP is then self‐drivenly hydrolyzed into non‐toxic products by environmental moisture, achieving 91.5% degradation efficiency. Utilizing the solution processability of HOFs, functional textiles that show an immediate color change upon DCP exposure are produced. This work establishes a rational design strategy for multifunctional HOF systems that synergistically integrate capture, detection, and degradation for effective threat mitigation. FDU‐HOF‐5, an enzyme‐inspired hydrogen‐bonded framework, enables targeted capture, real‐time visual alert, and detoxification of nerve agent simulants through biomimetic sites and multivalent interactions. Integrable into protective gear, it pioneers on‐site threat monitoring strategies for persistent neurotoxic hazards, advancing smart, responsive materials in public safety.

Background The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. Methods Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. Discussion The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. Trial registration ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Background Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. Methods Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. Discussion The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. Trial registration ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the development of OA. Lentinan, a type of polysaccharide derived from Lentinus edodes, has been demonstrated to possess significant anti-viral, anti-cancer, and anti-inflammatory effects, and has been recently used in the treatment of several inflammatory diseases. However, little research has focused on the pharmacological effect of lentinan in human OA. We evaluated the anti-inflammatory and anti-ROS effects of lentinan in SW1353 chondrocytes treated with AGEs using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and the nitro oxide-specific stain DAF-FM DA. The regulatory effects of lentinan on NF-κB and MAPK p38 signaling were investigated via promoter assay and Western blot analysis. We found that lentinan inhibits the production of pro-inflammatory cytokines, including IL-1β, TNF-α, IL-8 and the secretion of PGE and NO, by reducing the expression of COX-2 and iNOS in AGE-challenged chondrocytes. Lentinan also reduces AGE-induced increased expression of matrix metalloproteinases-1, -3, and -13 (MMP-1, MMP-3, MMP-13). Furthermore, lentinan has a similar effect on a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4, ADAMTS-5). Mechanistically, lentinan reduces the activation of NF-κB. Our findings indicate that lentinan shows a protective effect against AGE-induced inflammatory response in chondrocytes. These findings suggest that lentinan is a promising agent for the treatment of OA that could be used as a dietary supplement for patients with OA.

Background and AimVascularity is a critical feature in the evaluation of pancreatic neuroendocrine tumor (PNET). When done by EUS, contrast agents are recommended. However, vascular architecture (VA) can also be evaluated by routine Doppler flow in EUS without contrast agents. Our aim was to provide a simple VA classification in EUS for PNET grade and prognosis.MethodsAll pathologically proven PNET cases with EUS between 2012 and 2018 were retrospectively analyzed. The Doppler imaging was retrieved for VA classification. Predictive model construction was performed by machine learning algorithms.ResultsA total of 112 PNET cases were evaluated, among which 93 cases were subjected to VA classification. The VA was classified into type A (peritumoral with or without intratumoral vessels [A1 or A2]); type B (only intratumoral vessels); and type C (flow was absent). The VA classification was significantly correlated with tumor grades: 74% type A1 was G1, 73% type B was G2, and 58% type C was G3. Multivariate analysis indicated that elevated serum CA19-9 and type C classification were the independent predictors of G3 tumor. Five machine learning models were constructed, among which random forest was the best one with an AUC of 0.9972. Low-risk patients classified by this model exhibited better prognosis than high-risk patients (p = 0.0087).ConclusionsIn the novel simple VA classification, peritumoral, intratumoral, and absent vessels are prone to be G1, G2, and G3, respectively. Combined with serum CA19-9 and lesion size, the VA classification could predict tumor grade and prognosis in PNET.

Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety.

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive cancers, with low rates of durable response to chemoradiotherapy and limited therapeutic options for relapsed disease. To uncover mechanisms of treatment resistance and relapse, we performed comprehensive multi-omics profiling of >100 pre-treatment and post-relapse ESCC tumors from a prospective clinical trial (NCT04694391), integrating whole-exome/genome sequencing, bulk RNA-sequencing, single-cell RNA sequencing, and spatial transcriptomics. We identify somatic alterations in NFE2L2/KEAP1 in nearly 40% of relapsed patients, which are associated with upregulation of NRF2 signaling targets in resistant tumors and cell line models. At single-cell and spatial resolution, relapsed tumors are enriched for NRF2-activated epithelial cells that physically co-localize with immunosuppressive SPP1⁺TREM2⁺ macrophages. This co-localization suggests a synergistic interaction between NRF2-driven tumor programs and macrophage-mediated immune suppression that promotes relapse after chemoradiotherapy. Our findings nominate NFE2L2/KEAP1 mutations as predictive biomarkers for patient stratification and highlight therapeutic targeting of NRF2 signaling and SPP1⁺TREM2⁺ macrophages as rational strategies to overcome resistance in ESCC.Competing Interest StatementH.L. is a shareholder and scientific advisor of Precision Scientific Ltd.