Background Limited literature exists supporting the use of a needle-free injection system (NFIS) for in vitro fertilization (IVF) cycles, highlighting an unmet need for painless drug delivery to improve patient compliance and reduce treatment dropouts. We evaluated the effectiveness and patient compliance of NFIS for administering gonadotropins for controlled ovarian stimulation (COS) in IVF-embryo transfer (IVF-ET) cycles. Methods This real-world study included female patients aged ≥21 years who underwent COS in IVF-ET cycles from December 2025 to February 2026. Patients received either recombinant follicle-stimulating hormone (r-FSH) (Group-1) or r-FSH with highly purified human menopausal gonadotropin (hMG) (Group-2). The endpoints were the number of mature oocytes and total oocytes retrieved, total dose of gonadotropins used, total number of days of stimulation, serum FSH levels (on day 6 of stimulation and on the day of trigger), total number of follicles >17 mm on the day of trigger, and pain score. Results Of 43 patients analyzed (Group-1: 25; Group-2: 18), the mean ± SD total number of days of ovarian stimulation was 10.0 ± 1.2, and the total dose of gonadotropins used was 2458.7 ± 617.8 IU. The total number of days of ovarian stimulation was 10.0 ± 1.0 and 10.1 ± 1.5, and the total dose of gonadotropins used was 2203.9 ± 554.2 IU and 2812.5 ± 530.5 IU, for Group-1 and Group-2, respectively. Similarly, serum FSH levels at day 6 of COS were 18.1 ± 4.4 and 27.8 ± 0.0 IU/L, and on the day of ovulation trigger were 15.8 ± 6.0 and 36.0 ± 28.3 IU/L. Total number of follicles >17 mm on the day of trigger was 12.2 ± 6.5 in Group-1 and 4.8 ± 4.1 in Group-2. Total number of oocytes was 13.4 ± 6.2 and 6.1 ± 7.6, and the total number of metaphase II oocytes retrieved was 11.0 ± 5.4 and 4.8 ± 6.3 for Group-1 and Group-2, respectively. The pain score for administering r-FSH via NFIS in both groups was 1.2 ± 1.3, and for hMG via NFIS in Group-2, it was 3.6 ± 2.2. Conclusion NFIS was effective for administering gonadotropins for COS in IVF-ET cycles while ensuring patient compliance with minimal pain.

The gut microbiota plays a pivotal part in human health, yet the molecular mechanisms that underlie its effects are largely unexplored. Bacteroides, a dominant genus in the human gut microbiota, is depleted in patients with atherosclerosis[1], but its causal relationship with disease remains unclear. Here, using a mouse model, we show that administration of Bacteroides uniformis alleviates atherosclerosis through the upregulation of hepatic low-density lipoprotein receptor expression. Bioactivity-guided screening revealed pentadecanoic acid (PA, C15:0), a saturated odd-chain fatty acid, as a principal bioactive metabolite. PA supplementation reduced atherosclerotic plaque burden by around 50% and significantly improved plasma lipid profiles, a result that underscores its therapeutic potential. Mechanistically, PA enhances cholesterol clearance by directly inhibiting HMG-CoA reductase, suppressing hepatic cholesterol biosynthesis and promoting plasma low-density lipoprotein cholesterol removal. Analyses of 100 gut bacterial strains revealed that PA production occurs across multiple Bacteroidota genera. Notably, PA is markedly depleted in patients with dyslipidaemia. In summary, a Bacteroidota-derived odd-chain fatty acid regulates gut-liver crosstalk, and modulation of the microbial-metabolic axis has atheroprotective potential.

Despite established roles in multiple cancers, the specific function and molecular mechanism of SRY-related HMG-box 5 (SOX5) remain elusive in esophageal squamous cell carcinoma (ESCC). SOX5 expression in ESCC tissues, its correlation with prognosis, and its relationship with toll-like receptor 4 (TLR4) and NOD-like receptor family pyrin domain containing 3 (NLRP3) were assessed with bioinformatic methods. Expression of SOX5 and TLR4 in ESCC cells was detected by quantitative reverse transcription polymerase chain reaction. In SOX5-overexpressing or TLR4-knockdown ESCC cells, cell death was evaluated by propidium iodide staining, migration and invasion were detected using Transwell assays, cell proliferation was assessed by colony formation assay, pyroptosis was observed using an optical microscope and confirmed using Annexin V/7-aminoactinomycin D staining, the binding of SOX5 to the TLR4 promoter was confirmed by chromatin immunoprecipitation assay, and the expression of key pyroptosis pathway proteins (Gasdermin D, Gasdermin D-N, cleaved Caspase-1 (c-CASP1), and NLRP3) was analyzed by Western blot. SOX5 downregulation in ESCC tissues and cells was observed and correlated with shorter survival in patients with ESCC. SOX5 expression positively correlated with the key pyroptosis pathway genes TLR4 and NLRP3. SOX5 overexpression promoted ESCC cell pyroptosis and enhanced sensitivity to cisplatin (DDP). Mechanistically, SOX5 interacted with the TLR4 promoter and upregulated key pyroptosis pathway proteins; TLR4 knockdown reduced the enhanced pyroptosis and DDP sensitivity observed in SOX5-overexpressing cells. SOX5 enhances DDP sensitivity in ESCC by mediating TLR4/NLRP3 expression to promote cell pyroptosis, providing novel insights for ESCC treatment. SIGNIFICANCE STATEMENT: SRY-related HMG-box 5 function in esophageal squamous cell carcinoma was uncovered. SRY-related HMG-box 5 regulated toll-like receptor 4/NOD-like receptor family pyrin domain containing 3 to mediate pyroptosis.

Polyunsaturated fatty acids (PUFAs), especially gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), can block HMG-CoA reductase activity and thus decrease cholesterol synthesis/formation. Cholesterol has antioxidant actions and thus reduces the formation of ROS (reactive oxygen species). In contrast, PUFAs augment the generation of ROS. PUFAs undergo peroxidation to form lipid peroxides that are toxic to tumor cells but not normal cells. GPX4 (glutathione peroxidase) reduces the formation of lipid peroxides and thus enhances tumor cell resistance to the tumoricidal actions of radiation, anticancer drugs, and immune checkpoint inhibitors (ICIs). Tumor cells have relatively high amounts of GPX4 and hence are resistant to lipid peroxide-induced ferroptosis/apoptosis. In contrast, normal cells can upregulate their GPX4 activity/content upon exposure to toxic lipid peroxides and hence are resistant to ferroptosis or apoptosis when supplemented with various PUFAs or exposed to radiation, anticancer drugs, and ICIs. Thus, PUFAs (especially GLA, AA, and DHA) are selectively toxic to tumors but not normal cells. Interferon-γ (IFN-γ) is secreted by CD8[+] T cells, and AA induces ferroptosis of tumor cells in an ACSL4 (the protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family)-dependent lipid peroxidation process. IL-6, TNF-α, and IFN-γ activate PLA2 to release AA from membrane lipids, which is then peroxidized to trigger apoptosis or ferroptosis of cancer cells. CD8[+] T cells/macrophages/TILs/NK cells and other immunocytes downregulate the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system x c - , and impair the uptake of cystine by tumor cells, because of which accumulation of toxic lipid peroxides occurs in the tumor cells, leading to their apoptosis/ferroptosis/necrosis. In C6 glioma cells, the inhibition of the cystine/glutamate (XC) antiporter and glutamate-cysteine ligase (GCL) results in inhibition of glutathione biosynthesis that leads to ferroptosis of cancer cells because of accumulation of toxic lipid peroxides. Thus, the lipid peroxidation process is at the center of tumor cell apoptosis/ferroptosis.

Recent benchmarks report that deep-learning-based genetic perturbation models fail to outperform uninformative baselines. Here we introduce a positive control baseline and metric calibration framework, showing-across 14 datasets and 18 metrics-that common benchmarking metrics (for example, mean squared error and Pearson Δ) are frequently miscalibrated, with reduced sensitivity to measure positive model performance. Under well-calibrated metrics, we find that deep-learning-based genetic perturbation models can outperform uninformative baselines.

Mitigating oxidative stress and inhibiting HMG-CoA reductase are key pharmacological strategies against hyperlipidemia. This study investigated bioactive fractions from Salvia hispanica L., as a multi-pronged therapeutic agent in a high-fat diet (HFD)-induced hyperlipidemia in rats. Animals received daily oral administration of a chia aqueous extract (CAE), protein isolate (CPI), or protein hydrolysate (CPH) at 400 mg/kg for 12 weeks, with atorvastatin as a positive control. This represents the first systematic comparison of three distinct chia-derived fractions for metabolic intervention. All three fractions significantly improved HFD-induced metabolic derangements. This therapeutic effect was underpinned by a dual mechanism. First, all fractions restored systemic redox homeostasis by reducing lipid peroxidation and bolstering endogenous antioxidant enzymes (SOD, CAT, GPx). Second, the phenolic-rich CAE, containing abundant catechin and quinic acid, exhibited cholesterol-lowering activity. The in silico molecular docking study revealed high-affinity binding of catechin to the catalytic site of HMG-CoA reductase (docking score: -7.616 kcal/mol), suggesting putative enzyme interaction. Our results provide compelling evidence that chia-derived fractions ameliorate hyperlipidemia through both significant antioxidant activity and putative interference with cholesterol biosynthesis, positioning them as a robust nutraceutical strategy for managing metabolic disorders.

Clubroot disease is caused by the obligate biotrophic protist Plasmodiophora brassicae and severely limits Chinese cabbage (Brassica rapa subsp. pekinensis) production. Infection is accompanied by extensive reprogramming of host carbon metabolism and starch accumulation in enlarged roots. ADP-glucose pyrophosphorylase (AGPase) catalyzes the first committed step of starch biosynthesis, but the upstream regulation of the Chinese cabbage small-subunit gene BrAGPS1 remains poorly understood. We cloned the promoter regions of BrAGPS1a (BraA07g007740.3.5C) and BrAGPS1b (BraA01g014740.3.5C) from the inbred line 'Chiifu-401-42'. PlantCARE analysis predicted core promoter motifs and putative cis-regulatory elements associated with hormone, stress, and light responses. A root cDNA library prepared from 1, 3, and 5 weeks post-inoculation (wpi) was screened by yeast one-hybrid (Y1H) using selected promoter fragments as baits to recover candidate promoter-associated proteins. The screen yielded 76 nonredundant library hits, 15 of which were annotated as proteins with potential transcriptional, DNA-binding, histone-binding, or chromatin-associated functions. Integration with an RNA-sequencing (RNA-seq) time course at 1, 2, 3, and 5 wpi identified 28 Y1H-derived genes that were differentially expressed at one or more time points. Five candidates-a calcium-dependent protein kinase (CPK), a basic leucine zipper (bZIP) transcription factor, a three-high-mobility-group-box (3×HMG-box) protein, and two Alfin1-like plant-homeodomain (PHD-domain) proteins-were selected on the basis of functional annotation and infection-responsive expression. Quantitative real-time PCR (qRT-PCR) confirmed distinct treatment- and time-dependent expression patterns but did not test DNA binding or regulatory function. This study provides a prioritized set of BrAGPS1 promoter-associated candidates and testable hypotheses for investigating the transcriptional control of starch metabolism during clubroot development. One-to-one Y1H back-assays, electrophoretic mobility shift assays, promoter transactivation tests, and genetic analyses are required to establish direct binding, regulatory direction, and biological function.

Statins are widely regarded as the gold standard first-line treatment for hyperlipidemia, as they inhibit HMG-CoA reductase in the liver. This effectively reduces LDL cholesterol levels and reduces cardiovascular risks, such as heart attack and stroke. Simvastatin is a well-established, effective, and cost-efficient statin for lowering LDL cholesterol and reducing cardiovascular risk. However, it causes myopathy, rhabdomyolysis, myalgia, constipation, kidney failure, headache, abdominal pain, diarrhoea, nausea, and increased blood sugar levels with its use and higher doses of 80 mg/day. To address this, a liposomal simvastatin formulation with particle sizes of 150-250 nm was developed for intravenous administration. This formulation can potentially accumulate in the liver via passive targeting via the RES, thereby enhancing hepatic uptake and improving safety. The liposome was formulated using the thin-film hydration method and optimised using a central composite design. The optimized formulation's vesicle size was 204.66 ± 2.84 nm, with a PDI of 0.27 and a zeta potential of -58.11 mV, indicating uniform distribution and high stability. In-vitro drug release demonstrated controlled release of up to 92.46% over 60 h. The cellular toxicity assay showed that the optimized liposome was 10 times safer than pure simvastatin. In-vivo, the liposomal formulation significantly reduced lipid levels after administration of a 5 mg/kg dose in Triton X-100-induced hyperlipidemic rats, outperforming marketed formulations and standard drugs. Simvastatin-liposomes are safe, stable, and a more potent alternative to traditional oral simvastatin, offering improved liver targeting and a reduced toxicity profile.

We read with interest the study by Kura et al [...].