Hypoglycemic peptide preparation from Bacillus subtilis fermented with Pyropia: Identification, molecular docking, and in vivo confirmation.

Hypoglycemic foods have attracted increasing research interest. This study prepared a hypoglycemic product from Bacillus subtilis fermented with Pyropia (PBP), which has promising industrial potential, and elucidated its hypoglycemic mechanism. The aqueous PBP solution was orange, with protein as the main functional component. In vivo experiments demonstrated that PBP could increase insulin secretion and inhibit α-glucosidase activity, resulting in a hypoglycemic effect superior to that of acarbose at the same dose. Molecular docking revealed that the peptides APPVDID, GPPDSPY, PPSSPRP, and SPPPPPA from PBP could inhibit both α-glucosidase and dipeptidyl peptidase-IV (DPP-IV) activities. Pro residues promoted PBP peptide binding to the hydrophobic pocket S1 of DPP-IV. Additionally, PBP reduced inflammation and promoted the growth of beneficial gut bacteria (Prevotellaceae_UCG_003, Lachnospiraceae_UCG_001). This study presents a novel approach for the high-value utilization of Pyropia and a new option for the production of hypoglycemic functional foods and medicines.

Recognition of MCF-7 breast cancer cells using native collagen probes: Collagen source effect.

Developing superior cancer cell recognition probes is crucial for the development of tumor therapy and cancer early screening materials. In this study, we first achieved effective recognition of MCF-7 breast cancer cells using natural collagen probes. Through cell adhesion, cancer cell selective capture, and flow cytometry techniques, the binding efficiency of mammalian-derived collagens (bovine Achilles tendon collagen, porcine skin collagen) and fish-derived collagens (turbot skin collagen, grass carp skin collagen, mandarin fish skin collagen) to cancer cells (MCF-7 breast cancer cells) and normal cells (human umbilical vein endothelial cells, HUVECs) was analyzed and compared. The feasibility of different source collagens as probes for recognition of MCF-7 cells was explored in vitro. The results indicated that mammalian-derived collagens had a superior advantage over fish-derived collagens in recognizing MCF-7 cells, with bovine Achilles tendon collagen achieving a capture rate of up to 64.7 % in a multicellular co-culture system. Furthermore, in vivo imaging of BALB/c tumor-bearing mice confirmed the high-efficiency targeted recognition performance of the bovine Achilles tendon collagen probe for MCF-7 cells.

HyperArc radiotherapy for recurrent synovial sarcoma of infratemporal fossa: a rare case report and review of the literature.

Background: Synovial sarcoma (SS), a malignant and uncommon soft tissue sarcoma, typically manifests in the extremities and trunk. However, its occurrence in the infratemporal fossa (ITF) of the head and neck is exceedingly rare. Patients afflicted with SS in this anatomical region pose considerable challenges, as radical surgery is often difficult to undertake, leading to a high rate of postoperative recurrence. Moreover, it is often difficult to effectively control the tumor when the cancer relapses. Much of our understanding regarding SS of ITF stems from limited case reports, with a lack of established clinical guidelines for its management. There exists a significant clinical need for effective therapeutic approaches. Case Description: This case report documents a patient with SS of ITF, experiencing repeated recurrences despite undergoing multiple surgeries and chemotherapy treatments. The patient underwent HyperArc (HA) radiotherapy (RT) in conjunction with concurrent chemotherapy utilizing cisplatin, resulting in a remarkable 3-year follow-up period devoid of recurrence. Conclusions: The primary objective of this case report is to disseminate knowledge regarding this rare manifestation of SS of ITF, detailing the successful treatment strategy employed. In this case, we employed a comprehensive treatment strategy involving concurrent chemoradiotherapy based on HA. Our findings demonstrate that this approach was effective in achieving disease control and improving patient outcomes.

In situ/operando method for energy stability measurement of synchrotron radiation.

A novel in situ/operando method is introduced to measure the photon beam stability of synchrotron radiation based on orthogonal diffraction imaging of a Laue crystal/analyzer, which can decouple the energy/wavelength and Bragg angle of the photon beam using the dispersion effect in the diffraction process. The method was used to measure the energy jitter and drift of the photon beam on BL09B and BL16U at the Shanghai Synchrotron Radiation Facility. The experimental results show that this method can provide a fast way to measure the beam stability of different light sources including bending magnet and undulator with meV-level energy resolution and ms-level time response.

Tensile Constitutive Model of Engineered Cementitious Composites Reinforced by High-Strength Steel Wire Mesh.

The presentation of a constitutive model could help researchers to predict the mechanical behavior of a material, which also contributes to the further generalization of the material. This paper is to explore the tensile constitutive model of engineered cementitious composites (ECCs) reinforced by high-strength steel wire mesh based on experiments and numerical simulations. DIANA was used to simulate the tensile process of the specimens, and experiments were carried out to validate the numerical model. The effect of the ECCs' tensile strength, reinforcement ratio and specimen size were considered during the specimen design process. The results showed that most of the errors of the simulated values compared to the experimental results were within 5%, which proved that the numerical model was quite accurate. The proposed constitutive model revealed the different roles played by ECCs and high-strength steel wires at different stress stages, and the calculation results were in high agreement with the simulation results, indicating the effectiveness of the constitutive model. The study in this paper could provide an important reference for the popularization and application of ECCs reinforced by high-strength steel wire mesh.

Adipocyte-derived glutathione promotes obesity-related breast cancer by regulating the SCARB2-ARF1-mTORC1 complex.

Obesity is a major risk factor for poor breast cancer outcomes, but the impact of obesity-induced tumor microenvironment (TME) metabolites on breast cancer growth and metastasis remains unclear. Here, we performed TME metabolomic analysis in high-fat diet (HFD) mouse models and found that glutathione (GSH) levels were elevated in the TME of obesity-accelerated breast cancer. The deletion of glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in GSH biosynthesis, in adipocytes but not tumor cells reduced obesity-related tumor progression. Mechanistically, we identified that GSH entered tumor cells and directly bound to lysosomal integral membrane protein-2 (scavenger receptor class B, member 2 [SCARB2]), interfering with the interaction between its N and C termini. This, in turn, recruited mTORC1 to lysosomes through ARF1, leading to the activation of mTOR signaling. Overall, we demonstrated that GSH links obesity and breast cancer progression by acting as an activator of mTOR signaling. Targeting the GSH/SCARB2/mTOR axis could benefit breast cancer patients with obesity.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) for gemcitabine.

BACKGROUND: Gemcitabine is widely used in the treatment of various cancers. This study aims to evaluate gemcitabine-associated adverse events (AEs) using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: We analyzed data spanning from January 2004 to June 2023. Employing reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms, we identified AEs with positive signals in patients administered gemcitabine. RESULTS: Out of 16,623,939 reports, 23,645 involved gemcitabine as the 'primary suspected (PS)' resulting in 74,306 AEs. Consistent with the reports in the specification and clinical trials, thrombocytopenia, pyrexia, neutropenia, and anemia were the most common AEs. Notably, our study identified some unexpected AEs such as abdominal pain, pleural effusion, ascites, and gastrointestinal hemorrhage, among others. The most significant SOC was 'Blood and lymphatic system disorders'. The median onset time for gemcitabine-related AEs was 24 days (interquartile range [IQR] 6-82 days), with most cases occurring within the initial 30 days following gemcitabine administration. CONCLUSION: Gemcitabine is associated with a broad spectrum of AEs affecting multiple organ systems, with a notable incidence of hospitalization. The study highlights both expected and unexpected AEs, which could enhance future clinical applications and safety of gemcitabine.

Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum.

Silicon dioxide (SiO2) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO2 particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO2 particles of three sizes (1 µm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO2 particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO2 particles. This study elucidates the toxicological mechanism of SiO2 particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO2 particles to humans.

Effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.

BACKGROUND: Following cesarean section, a significant number of women encounter moderate to severe pain. Inadequate management of acute pain post-cesarean section can have far-reaching implications, adversely impacting maternal emotional well-being, daily activities, breastfeeding, and neonatal care. It may also impede maternal organ function recovery, leading to escalated opioid usage, heightened risk of postpartum depression, and the development of chronic postoperative pain. Both the Chinese Enhanced Recovery After Surgery (ERAS) guidelines and the American ERAS Society guidelines consistently advocate for the adoption of multimodal analgesia protocols in post-cesarean section pain management. Esketamine, functioning as an antagonist of the N-Methyl-D-Aspartate receptor, has been validated for pain management in surgical patients and has exhibited effectiveness in depression treatment. Research has suggested that incorporating esketamine into postoperative pain management via pain pumps can lead to improvements in short-term depression and pain outcomes. This study aims to assess the efficacy and safety of administering a single dose of esketamine during cesarean section. AIM: To investigate the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section. METHODS: A total of 315 women undergoing elective cesarean section under combined spinal-epidural anesthesia were randomized into three groups: low-dose esketamine (0.15 mg/kg), high-dose esketamine (0.25 mg/kg), and control (saline). Postoperative Visual Analog Scale (VAS) scores were recorded at 6 hours, 12 hours, 24 hours, and 48 hours. Edinburgh Postnatal Depression Scale (EPDS) scores were noted on 2 days, 7 days and 42 days. Ramsay sedation scores were assessed at specified intervals post-injection. Postoperative adverse reactions were also recorded. RESULTS: Low-dose group and high-dose group compared to control group, had significantly lower postoperative VAS pain scores at 6 hours 12 hours, and 24 hours (P < 0.05), with reduced analgesic usage (P < 0.05). EPDS scores and postpartum depression rates were significantly lower on 2 days and 7 days (P < 0.05). No significant differences in first exhaust and defecation times were observed (P > 0.05), but ambulation times were shorter (P < 0.05). Ramsay scores were higher at 5 minutes, 15 minutes, and upon room exit (P < 0.05). Low-dose group and high-dose group had higher incidences of hallucination, lethargy, and diplopia within 2 hours (P < 0.05), and with low-dose group had lower incidences of hallucination, lethargy, and diplopia than high-dose group (P < 0.05). CONCLUSION: Esketamine enhances analgesia and postpartum recovery; a 0.15 mg/kg dose is optimal for cesarean sections, balancing efficacy with minimized adverse effects.

[Comparative study of total hip arthroplasty with and without femoral osteotomy in Crowe â £ developmental dysplasia of the hip].

OBJECTIVE: To compare the clinical effects of total hip arthroplasty(THA) with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH). METHODS: The data on 46 patients who underwent THA for unilateral Crowe Ⅳ DDH between 2012 and 2017 were analyzed retrospectively. They were divided into two groups according to the different surgical methods. There were 24 patients in the osteotomy group, 3 males and 21 females, with an average age of (47.3±9.0) years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group, 2 males and 20 females, with an average age of (51.6±8.3) years old ranged from 40 to 61 years old. The operative time, bleed loss, postoperative drainage volume, postoperative complications, ROM of hip, Harris hip score, limb length discrepancy(LLD), and radiological data were recorded. The femoral dislocation height and the implantation depth of sleeve were measured. RESULTS: All patients were followed up. The mean follow-up time was (3.8±1.2) years ranged from 2 to 6 years in the osteotomy group and (3.2±0.9) years ranged from 1 to 5 years in the non-osteotomy group. The operative time(136.8±18.9) min, bleed loss (709.8±89.4) ml, postoperative drainage volume(308.8±98.2) ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min, (516.5±103.3) ml, (245.3±79.3) ml (P<0.05). The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups (P<0.05), but there was no significant difference between two groups (P>0.05). The LLD at last follow up was significantly increased compared with preoperative LLD in two groups, the LLD in non-osteotomy group(0.7±0.2) cm showed signifcant smaller than the two osteotomy group(1.2±0.4) cm. Between osteotomy and non-osteotomy groups, the preoperative range of motion of hip joint [(89.5±19.7) °vs (102.5±16.8) °], the preoperative height of dislocation of femoral head [(4.56±0.61) cm vs (3.10±0.73) cm], the proximal implant depth of S-ROM [(0.93±0.36) cm vs (1.67±0.28) cm] was significantly different (P<0.05). Eleven patients in the osteotomy group still had claudication, and 4 patients in the non-osteotomy group had mild claudication (P<0.05). In non-osteotomy group, 3 patients developed nerve injury (1 patient of sciatic nerve, 2 patients of femoral nerve) and 1 case developed periprosthetic fracture. In osteotomy group, 2 case of dislocation and 2 cases of periprosthetic fractures. CONCLUSION: Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD. However, osteotomy is more complex and time-consuming, limb length difference is greater, and the incidence of claudication is higher. Furthermore, patients with smaller preoperative hip mobility, higher femoral dislocation, limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

Effects of functional groups on ESIPT and antioxidant activity of apigenin: A non-existent enol* state fluorescein.

The development and enhancement of antioxidant drugs, which are aimed at mitigating DNA damage, mutations, and cancer, are of paramount significance in the biomedical sphere. In recent years, antioxidant drug molecules with photoluminescence have sprung up like mushrooms. Apigenin (AP), characterized by its distinctive property of excited state intramolecular proton transfer (ESIPT), plays a pivotal role in mediating antioxidant and anticancer activities. Despite being a representative molecule of the non-existent enol form (E*) state with ESIPT nature, there is a notable lack of theoretical investigations into its antioxidant properties. Herein, density functional theory (DFT) and time-dependent DFT methodologies were utilized to explore the effects of various functional groups on AP molecules in a methanol solvent. Studies have demonstrated that for the non-existent E* state fluorescence molecule AP, the ESIPT process can significantly enhance the antioxidant potency of AP and its derivatives. However, the introduction of electron-withdrawing groups significantly accelerated the ESIPT process while simultaneously suppressing the antioxidant activity of AP-CN. Conversely, the incorporation of electron-donating groups effectively inhibited the ESIPT process, yet markedly enhanced the antioxidant activity of AP-NH2. This investigation furnishes vital perspectives and sources of reference for the conception and advancement of groundbreaking antioxidant medications that aim to tackle non-existent E* state molecules.

WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc.

The dysfunction of the ubiquitin-proteasome system (UPS) facilitates the malignant progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy has been proposed, identifying effective targets has been challenging. In this study, we conducted a focused screen of siRNA libraries targeting UPS-related WD40 repeat (WDR) proteins and found that silencing WDR20, a deubiquitinating enzyme activating factor, selectively inhibited the proliferation of HCC cells without affecting normal hepatocytes. Moreover, the downregulation of WDR20 expression induced HCC cellular senescence and suppressed tumor progression in xenograft, sleeping beauty transposon/transposase, and hydrodynamic tail vein injection-induced HCC models, and Alb-Cre+/MYC+ HCC transgenic mouse models. Mechanistically, we found that WDR20 silencing disturbed the protein stability of c-Myc, orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc, thereby promoting the transcriptional activation of CDKN1A. Further investigation revealed a positive coexpression of WDR20 and c-Myc in a tissue microarray with 88 HCC clinical samples. By employing three patient-derived organoids from individuals with HCC, we have validated the decrease in c-Myc expression and the significant induction of senescence and growth inhibition following silencing of WDR20. This study not only uncovers the biological function of WDR20 and elucidates the molecular mechanism underlying its negative regulation of HCC cellular senescence but also highlight the potential of WDR20 as a promising target for HCC therapy.

Noise & mottle suppression methods for cumulative Cherenkov images of radiation therapy delivery.

PURPOSE: Cherenkov imaging during radiotherapy provides a real time visualization of beam delivery on patient tissue, which can be used dynamically for incident detection or to review a summary of the delivered surface signal for treatment verification. Very few photons form the images, and one limitation is that the noise level per frame can be quite high, and mottle in the cumulative processed images can cause mild overall noise. This work focused on removing or suppressing noise via image postprocessing. APPROACH: Images were analyzed for peak-signal-to-noise and spatial frequencies present, and several established noise/mottle reduction algorithms were chosen based upon these observations. These included total variation minimization (TV-L1), non-local means filter (NLM), block-matching 3D (BM3D), alpha (adaptive) trimmed mean (ATM), and bilateral filtering. Each were applied to images acquired using a BeamSite camera (DoseOptics) imaged signal from 6x photons from a TrueBeam linac delivering dose at 600 MU/min incident on an anthropomorphic phantom and tissue slab phantom in various configurations and beam angles. The standard denoised images were tested for PSNR, noise power spectrum (NPS) and image sharpness. RESULTS: The average peak-signal-to-noise ratio (PSNR) increase was 17.4% for TV-L1. NLM denoising increased the average PSNR by 19.1%, BM3D processing increased it by12.1% and the bilateral filter increased the average PSNR by 19.0%. Lastly, the ATM filter resulted in the lowest average PSNR increase of 10.9%. Of all of these, the NLM and bilateral filters produced improved edge sharpness with, generally, the lowest NPS curve. CONCLUSION: For cumulative image Cherenkov data, NLM and the bilateral filter yielded optimal denoising with the TV-L1 algorithm giving comparable results. Single video frame Cherenkov images exhibit much higher noise levels compared to cumulative images. Noise suppression algorithms for these frame rates will likely be a different processing pipeline involving these filters incorporated with machine learning.

Andrographolide: A promising therapeutic agent against organ fibrosis.

Fibrosis is the terminal pathology of chronic illness in many organs, marked by excessive accumulation of extracellular matrix proteins. These changes influence organ function, ultimately resulting in organ failure. Although significant progress has been achieved in comprehending the molecular pathways responsible for fibrosis in the last decades, effective and approved clinical therapies for the condition are still lacking. Andrographolide is a diterpenoid isolated and purified mainly from the aboveground parts of the Andrographis paniculata plant, which possesses good effects of purging heat, detoxifying, antibacterial and anti-inflammatory. In-depth research has gradually confirmed the anticancer, antioxidant, antiviral and other effects of Andro so that it can play a preventive and therapeutic role in various diseases. Over the past few years, an increasing number of research findings have indicated that Andro exerts antifibrotic effects in various organs by acting on transforming growth factor-ß/small mother against decapentaplegic protein, mitogen-activated protein kinases, nuclear factor-E2-related factor 2, nuclear factor kappa-B and other signalling molecules to inhibit inflammation, oxidative stress, epithelial-mesenchymal transition, fibroblast activation and collagen buildup. This review presents a compilation of findings regarding the antifibrotic impact of Andro in tissue and cell models in vitro and in vivo. Emphasis is placed on the potential therapeutic benefits of Andro in diseases related to organ fibrosis. Existing studies and cutting-edge technologies on Andro pharmacokinetics, toxicity and bioavailability are briefly discussed to provide evidence for accelerating its clinical conversion and adoption.

Targeted sonodynamic therapy induces tumor cell quasi-immunogenic ferroptosis and macrophage immunostimulatory autophagy in glioblastoma.

In this study, we demonstrated the mechanism of a glioblastoma (GBM)-targeted sonodynamic therapy (SDT) strategy employing platelets loaded with a sonosensitizer based on functionalized boron nitride nanoparticles carrying chlorin e6 (BNPD-Ce6). In the in vitro study, we first found that the BNPD-Ce6-mediated sonodynamic action (SDA) induced remarkable viability loss, DNA damage, and cell death in the GBM cells (GBCs) but not macrophages. Surprisingly, the SDA-exposed GBCs displayed a ferroptotic phenotype while the SDA-exposed macrophages underwent immuno-stimulatory autophagy and potently potentiated the SDA's toxicity to the GBCs. The ferroptotic GBCs induced by the SDA were found to be quasi-immunogenic, characterized by the emission of some alarmins such as ATP, HSP90, and CRT, but absent HMGB1, a potent endogenous adjuvant. As such, the SDA-stressed GBCs were unable to stimulate the BMDMs. This defect, interestingly, could be rescued by platelets as a donor of HMGB1 which markedly enhanced the BNPD-Ce6's sonotoxicity to the GBCs. In the in vivo study, we first employed BNPD-Ce6-loaded platelets to achieve ultrasound-triggered, targeted delivery of BNPD-Ce6 in grafted intra-cranial GBMs and subsequent sonodynamic tumor damage. An SDT regimen designed based on these results slowed the growth of grafted intra-cranial GBMs and significantly increased the survival of the host animals. Pathological examination of the SDT-treated GBMs revealed tissue necrosis and destruction and validated the in vitro observations. Finally, the depletion of macrophages was found to abrogate the efficacy of the SDT in subcutaneous GBC grafts. In conclusion, the BNPD-Ce6@Plt-mediated SDT is a practicable and efficacious anti-GBM therapy. Its therapeutic mechanism critically involves a synergy of tumor cell ferroptosis, macrophage stimulation, and platelet activation induced by the SDA.

Review effects of radiation treatment on HPV-related vulvar cancer: a meta-analysis and systematic review.

Objective: Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods: A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results: We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (M-H=4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion: In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials.

Bioactive polyketides and tryptophol alkaloids from the endophytic fungus Botryosphaeria dothidea LE-07 of Chinese tulip tree.

Two new tetraketide-derived phenol rhamnosides [botryrhamnosides A (1) and B (2)] and a new rhamnosylated tryptophol alkaloid (botryrhamnoside C, 3), along with seven related known compounds (4-10) were isolated from the solid culture of Botryosphaeria dothidea LE-07, an endophytic fungus residing in the leaves of the rare medicinal plant Chinese tulip tree (Liriodendron chinense). Their structures with the absolute configurations were determined by a combination of spectroscopy methods, comparing specific rotations, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 are rare tetraketide-derived resorcinols incorporating a l-rhamnose moiety, while 3 represents the first example of rhamnose-bound tryptophol derivatives produced by microorganisms. These metabolites were evaluated in vitro for their antimicrobial and anti-neuroinflammation activities. The rhamnosylated derivatives 1-5 displayed potent antibacterial activity against Escherichia coli, with MIC values in the range of 8-16 µg/mL. Compound 2 attenuated neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 microglial cells, by decreasing the level of pro-inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)] and down-regulating the mRNA expression of inducible nitric oxide synthase (iNOS). In addition, compound 8 exhibited remarkable inhibitory effect against the ATP-citrate lyase (ACL), an emerging drug target for hyperlipidemia and related glycolipid metabolic disorders, with an IC50 value of 5.32 µM.

The critical role of Gαi3 in oral squamous cell carcinoma cell growth.

The identification of novel and effective therapeutic targets for oral squamous cell carcinoma (OSCC) is of paramount importance. This study investigates the expression, potential functions, and mechanistic insights of G protein inhibitory subunit 3 (Gαi3) in OSCC. Gαi3 is found to be upregulated in human OSCC tissues as well as in various primary and established OSCC cells. In different OSCC cells, silencing of Gαi3 through shRNA resulted in inhibited cell proliferation and migration, while also inducing apoptosis. Knockout (KO) of Gαi3 via the CRISPR/Cas9 method produced significant anti-cancer effects in OSCC cells. Conversely, ectopic overexpression of Gαi3 enhanced OSCC cell growth, promoting cell proliferation and migration. Gαi3 plays a crucial role in activating the Akt-mTOR signaling pathway in OSCC cells. Silencing or KO of Gαi3 led to decreased phosphorylation levels of Akt and S6K, whereas overexpression of Gαi3 increased their phosphorylation. Restoration of Akt-mTOR activation through a constitutively active mutant Akt1 mitigated the anti-OSCC effects induced by Gαi3 shRNA. In vivo, Gαi3 silencing significantly suppressed the growth of subcutaneous OSCC xenografts in nude mice, concomitant with inactivation of the Akt-mTOR pathway and induction of apoptosis. Collectively, these findings underscore the critical role of Gαi3 in OSCC cell growth both in vitro and in vivo.

Novel computed tomography-based nomograms for the pretherapeutic prediction of response to neoadjuvant chemotherapy with S-1 and oxaliplatin with or without the addition of docetaxel in patients with advanced gastric cancer.

Background: Selecting the appropriate preoperative neoadjuvant chemotherapy (NACT) regimen for patients with advanced gastric cancer (GC) is critical to effective treatment. The aim of this study was to develop nomograms based on pretherapeutic computed tomography (CT) features to predict response to NACT with S-1 and oxaliplatin (SOX) or that with docetaxel and SOX (DOS) in patients with advanced GC. Methods: This study enrolled 311 consecutive patients with confirmed advanced GC undergoing contrast-enhanced CT before and after the three cycles of NACT with DOS (n=152) or SOX (n=159), who were randomized into a training cohort (TC) (NACT with DOS: n=111; NACT with SOX: n=120) and validation cohort (VC) (NACT with DOS: n=41; NACT with SOX: n=39). The objective response rate (ORR) was used to evaluate the response to NACT. In the TC, ORR was compared between the DOS and SOX regimens, and independent predictors including CT features and tumor differentiation were determined by univariate and binary logistic regression analyses. Individual nomograms were constructed for the SOX and DOS regimens in the TC, and the predictive accuracy was validated in the VC. Results: After NACT, the percentage of ORR was higher in patients receiving DOS than in those receiving SOX in TC (P value <0.05). The independent predictors after DOS and SOX were pretherapeutic cT stage [odds ratio (OR) =7.364; OR =8.848], cN stage (OR =1.027; OR =1.345), degree of differentiation (OR =7.127; OR =7.835), and gross tumor volume (OR =8.960; OR =8.161) (all P values <0.05). The concordance indexes of the individual nomograms developed using these predictors were 0.940 and 0.932 after DOS or SOX in the TC, respectively, which was validated by calibration plots with a slope close to 45° in the TC and VC. Conclusions: Despite there being a superior response to DOS compared with SOX, nomograms for predicting response to both NACT regimens were similar, with each demonstrating good predictive performance.