Efficacy and safety of serplulimab in solid tumors: a meta-analysis

ObjectiveThe goal of this study was to investigate the effectiveness and safety of serplulimab in advanced solid tumors through a meta-analysis approach.MethodsAn electronic search was conducted across the Embase, Web of Science, PubMed, and Cochrane Library databases, covering the period from each database’s inception through 6 May 2025. Meta-analysis and related analyses, including subgroup, sensitivity, and publication bias assessments, were performed using Stata 16.0. The Cochrane Risk of Bias Assessment Tool (version 5.1.0) was utilized to measure the quality of randomized controlled trials (RCTs). For single-arm studies, quality was evaluated using the Methodological Index for Non-Randomized Studies (MINORS).ResultsTen studies, including three RCTs and seven single-arm studies, were analyzed, involving 2,020 patients. In the analysis of RCTs, serplulimab significantly elevated overall survival (OS) [HR = 0.68, 95% CI: 0.59–0.79, P < 0.01], disease control rate (DCR) [RR = 1.04, 95% CI: 1.01–1.08, P < 0.05], progression-free survival (PFS) [HR = 0.53, 95% CI: 0.47–0.61, P < 0.01], and objective response rate (ORR) [RR = 1.30, 95% CI: 1.09–1.56, P < 0.01]. The analysis of single-arm studies revealed that the ORR for serplulimab in solid tumors was [ES = 45%, 95% CI: 31%–59%, P < 0.01], and the DCR was [ES = 71%, 95% CI: 63%–80%, P < 0.01]. Among the ten studies, the most common adverse events included reductions in platelet count (0.32, 95% CI: 0.20–0.43), white blood cell count (0.30, 95% CI: 0.17–0.44), anemia (0.29, 95% CI: 0.09–0.48), and proteinuria (0.28, 95% CI: 0.17–0.38).ConclusionBased on current research, serplulimab appears to be effective for solid tumors. However, given the limitations of the studies, for example, possible selection bias in single-arm studies, further multicenter, high-quality, large-sample RCTs are necessary to validate this conclusion

Reconstructing the regulatory circuit of cell fate determination in yeast mating response

Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our integrated experimental and modeling strategies could be widely applicable to other biological systems

Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways

Objective(s): Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin’s function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients’ serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway

Genome wide association study on feed conversion ratio using imputed sequence data in chickens

Objective Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genome-wide association study (GWAS) using sequence data imputed from single nucleotide polymorphism (SNP) panel in a Chinese indigenous chicken population. Methods A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K SNP genotyping array. Twenty-four birds were selected for sequencing, and the 600K SNP panel data were imputed to whole sequence data with the 24 birds as the reference. The GWAS were performed with GEMMA software. Results After quality control, 8,626,020 SNPs were used for sequence based GWAS, in which ten significant genomic regions were detected to be associated with FCR. Ten candidate genes, ubiquitin specific peptidase 44, leukotriene A4 hydrolase, ETS transcription factor, R-spondin 2, inhibitor of apoptosis protein 3, sosondowah ankyrin repeat domain family member D, calmodulin regulated spectrin associated protein family member 2, zinc finger and BTB domain containing 41, potassium sodium-activated channel subfamily T member 2, and member of RAS oncogene family were annotated. Several of them were within or near the reported FCR quantitative trait loci, and others were newly reported. Conclusion Results from this study provide valuable prior information on chicken genomic breeding programs, and potentially improve our understanding of the molecular mechanism for feeding traits

26Al/10Be burial dating and technological strategies of hominins at the Jijiazhuang Paleolithic site, Nihewan Basin, China: Implications for understanding Middle Pleistocene human adaptations in east Asia

With the discovery of more than a hundred Pleistocene Paleolithic sites, the Nihewan Basin of North China has become an area of reference for the study of human evolution and behavioral adaptations during and after the spread of hominins out of Africa and into Eurasia. However, most research has focused on the Early and Late Pleistocene archaeological record, whereas studies of the Middle Pleistocene sequence are relatively limited. Here we contribute to fill this gap by introducing the archaeological assemblage and 26Al/10Be burial dating of the newly discovered Jijiazhuang (JJZ) Paleolithic site. Systematic excavations in recent years have yielded well-preserved stone artifacts and mammalian fossils in fluvio-lacustrine sediments at the site. Cosmogenic 26Al/10Be burial dating indicates that hominins occupied the site between 0.49 ± 0.10 and 0.63 ± 0.11 Ma, corresponding to the extra-long interglacial period of MIS 15-13. The JJZ lithic assemblage shows evidence of relatively long-distance resource procurement, and the increased number of retouched tools indicate standardized, extensive and refined modification, even shaping strategies. The JJZ lithic technology shows advanced features that may shed light on the regional emergence of Middle Paleolithic technologies, in a paleoecological context where the extra-long duration of interglacial/mild stadial climate events (MIS 15−13) may have provided favorable conditions for increased technological capabilities among Middle Pleistocene hominins from the Nihewan Basin. Our study is the first to present a detailed techno-typological analysis of a Middle Pleistocene lithic assemblage in the Nihewan Basin and contributes to the characterization of technological adaptions in the high latitudes of East Asia.This research was supported by the National Natural Science Foundation of China ( 42371165 ), the National Key R&D Program of China (No. 2020YFC1521500 ), and an ERC-Advanced Grant (Horizon, 2020; BICAEHFID grant agreement No. 832980 )N

Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78–83%), high retention of cell viability (71–74%), high tumour cell enrichment against leukocytes (1.7–2 × 10^3), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4–0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research

On a Vision-Based Manipulator Simulator

This paper presents a typical grasp–hold–release micromanipulation simulator based on MATLAB and Simulink. Closed-loop force and position control were implemented only based on a camera. The work was mainly focused on control performance improvements and GUI design. Different types of control strategies were investigated in both the position and force control processes. Finally, incremental PID and positional PID were adopted in the gripper position control and force control processes, respectively. The best performance of the gripper position control was the fast response of 0.3 s without overshoot and steady-state errors in the range of 10–40 Hz. The new camera control algorithm kept a big motion range (4.48 × 4.48 mm) and a high position resolution of 0.56 µm, with a high force resolution of 1.56 µN in the force control stage. The maximum error between the measured force and the real force was maintained below 4 µN. The steady-state error and the setting time were less than 1.2% and less than 1.5 s, respectively. A separate app, the Image Generation Simulator app, was developed to assist users in getting suitable initial coordinates, camera parameters, desired position resolutions, and force resolutions, which are packed as a standalone executable file. The main app can run the simulation model, debug, playback, and report simulation results, and calculate the calibration equation. Different initial coordinates, camera parameters, sample frequencies, controller parameters, and even controller types can be adjusted from this app.</jats:p