TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study.

BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms. METHODS: Clinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms. RESULTS: A total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405-0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538-0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS. CONCLUSION: Preoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.

Prognostic significance of the novel immunonutritional marker of cholesterol-to-lymphocyte ratio in patients with non-metastatic breast cancer.

BACKGROUND: Although there is a strong correlation between the novel cholesterol-to-lymphocyte ratio (CLR) and tumor survival, its prognostic significance in breast cancer (BC) is unknown. After analyzing the relationship between CLR and the overall survival (OS) of patients with BC, we created a predictive model. METHODS: Following retrospective enrollment, 1316 patients with BC were randomized into two cohorts: validation (n = 392) and training (n = 924). Distinct factors within the training dataset were identified for OS by univariate and multivariate Cox analyses; two-tailed P-value < 0.05 were considered to indicate statistical significance. On this premise, we developed novel signals for survival prediction and utilized the calibration curve, receiver operating characteristic curves, and concordance index (C-index) to validate their efficacy across both datasets. RESULTS: Patients with BC were categorized into two categories with differing prognoses based on the CLR score [hazard ratio = 0.492; 95% confidence interval (CI): 0.286-0.846, P = 0.009]. A prediction nomogram was created based on multivariate analysis, which showed that N stage, postoperative pathological categorization, and CLR score were all independently correlated with OS. In the training [C-index = 0.831 (95% CI: 0.788-0.874)] and validation [C-index = 0.775 (95% CI: 0.694-0.856)] cohorts, the nomogram demonstrated favorable performance in predicting OS. In both the training and validation cohorts, it outperformed the traditional staging system [C-index = 0.702 (95% CI: 0.623-0.782)] and [C-index = 0.709 (95% CI: 0.570-0.847)]. The accurate prediction by the signature was further demonstrated by the time-dependent receiver operating characteristic curves. CONCLUSIONS: The novel immunonutritional marker CLR could function as a simplified, cost-effective, easily accessible, non-invasive, and readily promotive prognostic indicator for patients with early-stage BC and demonstrates superior predictive power than the traditional staging system.

Prognostic significance of platelet­to­albumin ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: a retrospective study of 858 cases.

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Identification and characterization of endogenous biomarkers for hepatic vectorial transport (OATP1B3-P-gp) function using metabolomics with serum pharmacology.

The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the drug. Unfortunately, there is still a lack of effective means to evaluate the disposal ability mediated by transporters. The present study was designed to identify a suitable endogenous biomarker for the assessment of OATP1B3-P-gp function in the liver. We established stably transfected HEK293T-OATP1B3 and HEK293T-P-gp cell lines. Results showed that azelaic acid (AzA) was an endogenous substrate for OATP1B3 and P-gp using serum pharmacology combined with metabolomics. There is a good correlation between the serum concentration of AzA and probe drugs of rOATP1B3 and rP-gp when rats were treated with their inhibitors. Importantly, after 5-fluorouracil-induced rat liver injury, the relative mRNA level and expression of rOATP1B3 and rP-gp were markedly down-regulated in the liver, and the serum concentration of AzA was significantly increased. These observations suggest that AzA is an endogenous substrate of both OATP1B3 and P-gp, and may serve as a potential endogenous biomarker for the assessment of the function of OATP1B3-P-gp for the prediction of changes in the pharmacokinetics of drugs transported by OATP1B3-P-gp in liver disease states.

Narrowband Organic/Inorganic Hybrid Afterglow Materials.

Narrowband afterglow materials display interesting functions in high-quality anti-counterfeiting and multiplexed bioimaging. However, there is still a limited exploration of these afterglow materials, especially for those with a full width at half maxima (FWHM) around 30 nm. Here, we report the fabrication of narrowband organic/inorganic hybrid afterglow materials via energy transfer technology. Coronene (Cor) with a long phosphorescence feature and broad phosphorescence band is selected as the donor for energy transfer, and inorganic quantum dots (QDs) of CdSe/ZnS with a narrowband emission are used as acceptors. Upon doping into the organic matrix, the resultant three-component materials exhibit a narrowband afterglow with an afterglow lifetime of approximately 3.4 s and an FWHM of 31 nm. The afterglow wavelength of the afterglow materials can be controlled by the QDs. This work based on organic/inorganic hybrids provides a facile approach for developing multicolor and narrowband afterglow materials, as well as opens a new way for expanding the features of organic afterglow for multifunctional applications. It is expected to rely on narrowband afterglow emitters to solve the "spectrum congestion" problem of high-density information storage in optical anti-counterfeiting and information encryption.

Phytochemical profiles, antioxidant activities, and synergistic antiproliferative effects of blueberry and apple peel extracts.

BACKGROUND: Blueberries and apples exhibit favorable bioactivity and health benefits as a result of their rich phytochemicals. Natural phytochemicals exist in complex forms, but there are few reports on whether have additive, synergistic or antagonistic effects between different phytochemicals. The present study aimed to elucidate the synergistic effects of blueberry extract (BE) and apple peel extract (APE) together with respect to inhibiting the proliferation of HepG2 liver cancer cells. Meanwhile, phytochemical characterization of BE and APE was conducted by HPLC, and total antioxidant activity was determined via a cellular antioxidant activity assay, oxygen radical absorption capacity assay and peroxy radical scavenging capacity assay. RESULTS: The results showed that BE and APE were rich in phytochemicals and had potent antioxidant activities, which synergistically inhibited cell proliferation. In the bilateral combination, the dose reduction index value increased by two-fold, and the combination index value at 95% inhibition was less than 1. Additionally, BE + APE supplementation could promote the expression levels of p53 and c-myc genes. In conclusion, the BE and APE had strong antioxidant activity and exhibited synergistic inhibition against proliferation of HepG2 cells. CONCLUSION: The present study can provide a theoretical basis for the synergistic effect of different phytochemicals in health care. © 2023 Society of Chemical Industry.

[Mechanism of aqueous extract of Strychni Semen in improving pain in rats with rheumatoid arthritis based on TLR4/TNF-α/MMP-9 signaling pathway].

This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). Venny 2.1.0 was used to obtain the common targets shared by Strychni Semen, RA, and pain, and STRING and Cytoscape 3.6.1 were used to build the protein-protein interaction network. Then, molecular docking was carried out in AutoDock Vina. Finally, the rat model of type Ⅱ collagen-induced arthritis(CIA) was established. The up-down method and acetone method were employed to examine the mechanical pain threshold and cold pain threshold of rats, and the pain-relieving effect of SA on CIA rats was evaluated comprehensively. Hematoxylin-eosin(HE) staining was employed to evaluate the histopathological changes of joints in CIA rats. The expression levels of key target proteins was determined by immunohistochemistry and Western blot, and the mRNA levels of key targets were determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). The results of network prediction showed that Strychni Semen may act on the TLR4/TNF-α/MMP-9 signaling pathway to exert the pain-relieving effect. The results of molecular docking showed that brucine, the main active component of SA, had strong binding ability to TLR4, TNF-α, and MMP-9. The results of animal experiments showed that SA improved the mechanical and cold pain sensitivity(P<0.05, P<0.01) and reduced the joint histopathological score of CIA rats(P<0.01). In addition, medium and high doses of SA down-regulated the protein and mRNA levels of TNF-α, TLR4, and MMP-9(P<0.05,P<0.01). In conclusion, SA alleviated the mechanical pain sensitivity, cold pain sensitivity, and joint histopathological changes in CIA rats by inhibiting the over activation of TLR4/TNF-α/MMP-9 signaling pathway.

Effects of Different Test Positions on Quantitative Muscle Strength of Wrist and Finger Flexor Muscle Groups and Its Standardization.

OBJECTIVES: To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group. METHODS: Forty healthy subjects (12 males and 28 females) were recruited. A portable digital quantitative muscle strength tester, Micro FET2TM, was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension, 0° neutral, and 30° flexion, respectively. Palmar abduction strength of the thumb was measured at 30° and 60°, respectively. Ten subjects were randomly selected from the 40 subjects, and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days. RESULTS: Except for the fact that in males, there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position, the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics：30° of wrist extension > neutral 0° position > 30° of flexion, and the PAST was 30°>60°; The flexor muscle strength of all the subjects was thumb > index finger > middle finger > ring finger > little finger; All muscle strength values of male were greater than those of female, and the difference was statistically significant (P<0.05); There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05). The reliability of muscle strength values measured at different times in 10 subjects was good. CONCLUSIONS: The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position, and a standardized and uniformed test position should be adopted in the actual identification. Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing. The 30° extension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint. The 30° position can be used as the best standardized test position for PAST.

Micronization induced gelatinization of tapioca starch and its effects on starch physicochemical and structural properties.

The vibrating superfine mill (VSM) is a machine that belongs to the micronization technique. In this study, VSM was employed to produce micronized tapioca starch by varying micronization times (15, 30, 45, and 60 min). The structural and physicochemical properties of the micronized starch were then examined. Scanning electron microscopy studies revealed that micronized starch was partially gelatinized, and the granule size dramatically increased when micronization time increased. X-ray diffraction patterns showed that the relative crystallinity was decreased from 24.67% (native) to 4.13% after micronization treatment for 15 min and slightly decreased after that. The solubility of micronized starch significantly increased as the micronization time increased, which was associated with the destruction of the starch crystalline structure. Differential scanning calorimetry investigations confirmed that micronized starch was "partly gelatinized," and the degree of gelatinization increased to 81.27% when the micronization time was 60 min. The weight-average molar mass was reduced by 15.0% (15 min), 30.9% (30 min), 55.7% (45 min), and 70.5% (60 min), respectively, indicating that the molecular structure was seriously degraded. The results demonstrated that the physicochemical changes of micronized starch granules were related to the destruction of the starch structure. These observations would provide details on micronized starch and its potential applications. PRACTICAL APPLICATION: These observations would provide details on micronized starch and its potential applications. Moreover, we believe that when the structures of starches were known, it is probable that the effect of VSM on the structural and physicochemical properties change of other starches might be predicted by adjusting the processing time.

Mg-Sr-Ca containing bioactive glass nanoparticles hydrogel modified mineralized collagen scaffold for bone repair.

The aim of this study is to explore the therapeutic effects of Mg-Sr-Ca containing bioactive glass nanoparticles sodium alginate hydrogel modified mineralized collagen scaffold (Mg-Sr-Ca-BGNs-SA-MC) on the repair of osteoporotic bone defect. During the study, Mg-Sr-Ca containing bioactive glass nanoparticles (Mg-Sr-Ca-BGNs) were synthesized using the sol-gel method, and the Mg-Sr-Ca-BGNs-SA-MC scaffold was synthesized by a simple method. The Mg-Sr-Ca-BGNs and the Mg-Sr-Ca-BGNs-SA-MC scaffold were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The elements of Mg, Sr, Ca and Si were effectively integrated into Mg-Sr-Ca-BGNs. SEM analysis revealed the presence of Mg-Sr-Ca-BGNs on the scaffold's surface. Furthermore, the cytotoxicity of the scaffolds were assessed using a live/dead assay. The result of the live/dead assay demonstrated that the scaffold materials were non-toxic to cell growth. More importantly, the in vivo study indicated that implanted scaffold promoted tissue regeneration and integration with newly formed bone. Overall, the Mg-Sr-Ca-BGNs-SA-MC scaffold is suitable for guided bone regeneration and beneficial to repair of osteoporotic bone defects.

Treatment of a patient with severe cerebral malaria during the COVID-19 pandemic in China: A case report.

BACKGROUND: On June 30, 2021, China received certification from the World Health Organization for malaria elimination. However, this certification does not signify the absence of malaria within China. Due to the increasing frequency of international exchanges and collaborations, the threat of imported malaria persists in China. Consequently, the prevention and control of imported malaria have become a primary focus for our country to maintain its malaria elimination status. CASE SUMMARY: Herein, we present a case report of a 53-year-old Chinese man who worked in Africa for nearly two years. He was diagnosed with malaria in the Democratic Republic of the Congo between November 19 and November 23, 2022. After receiving effective treatment with oral antimalarial drugs, his condition improved, allowing him to return to China. He was later admitted to our hospital on January 12, 2023, during the coronavirus disease 2019 pandemic in Huangshi, China. Through a thorough evaluation of the patient's symptoms, clinical signs, imaging and laboratory test results, and epidemiological data, he was rapidly diagnosed with severe cerebral malaria. The patient underwent successful treatment through a series of intensive care unit interventions. CONCLUSION: The successful treatment of this imported case of severe cerebral malaria provides a valuable reference for managing patients with similar malaria infections and has significant clinical implications.

Identification of the novel allele HLA-A*02:1144 in a Chinese platelet donor.

The novel HLA-A*02:1144 allele differs from HLA-A*02:03:01:01 by 3 nucleotides in exon 7.

Genomic full-length sequence of the HLA-B*40:86 allele identified in a Chinese individual.

HLA-B*40:86 differs from B*40:06:01:03 by a single nucleotide exchange in exon 3.

Structural characterization and human gut microbiota fermentation in vitro of a polysaccharide from Fucus vesiculosus.

In this study, an acidic polysaccharide (FVP-7 A) was isolated from Fucus vesiculosus by DEAE-Sepharose™ fast flow. The chemical composition, glycosidic bonds and in vitro fecal fermentation characteristics of FVP-7 A were studied. Results shown that FVP-7 A was a homogenous polysaccharide with average molecular weight of 30.94 kDa. Combined with FT-IR, monosaccharide composition, methylation and NMR analysis, the glycosidic bonds of FVP-7 A mainly composed of →4)-ß-D-Manp-(1→, →3)-α-L-Fucp-(1→, α-D-Manp-(1→, →3)-ß-D-Manp-(1 â†’ and →4,6)-α-D-Manp-(1→. The zeta potential and atomic force microscopy images indicated that FVP-7 A could exist stably as a single chain-like structure in dilute solution. After gut fermentation, FVP-7 A was utilized and promoted multiple short-chain fatty acids production, especially acetic acid, butyric acid and valeric acid. For prebiotics, FVP-7 A significantly increased the relative abundance of short-chain fatty acids producing bacteria such as Bacteroides, Lachnospira, Faecalibacterium, Ruminococcus, Oscillospira and Dialister, and inhiited the growth of the harmful bacteria Shigella. These results indicated that FVP-7 A could be used as a potential dietary supplement to improve intestinal health.

Enzymatically produced acylglycerol and glycerin monostearate additives improved the characteristics of gelatin-stabilized omega-3 emulsions and microcapsules.

The impacts of enzymatically produced acylglycerol and glycerin monostearate on the characteristics of gelatin-stabilized omega-3 emulsions and microcapsules were investigated. Tuna oil was enzymatically produced and the resulting acylglycerol was mixed with tuna oil at 12.5% (w/w) to prepare a novel oil phase. This oil phase was stabilized by gelatin to prepare oil-in-water emulsions and subsequent microcapsules via complex coacervation. The tuna oil with glycerin monostearate (GMS) at 1 and 2% (w/w) were used as controls. Results showed that both acylglycerol and GMS significantly reduced the emulsion droplet size and zeta potential, while increasing the viscoelasticity and stability. The diacylglycerol/monoacylglycerol were involved in the oil/water interfacial layer formation by lowering interfacial tension and increasing droplet surface hydrophobicity. Overall, the changed emulsion properties promoted the complex coacervation and contributed to the formation of microcapsules with improved oxidative stability. Therefore, enzymatically produced acylglycerol can develop high-quality stable omega-3 microencapsulated novel food ingredients.

VP5 protein of oncolytic herpes simplex virus type 2 induces apoptosis in A549 cells through TP53I3 protein.

Oncolytic virotherapy stands out as a burgeoning and promising therapeutic paradigm, harnessing the intrinsic cytotoxicity of oncolytic viruses for selective replication and dissemination within tumors. The primary mode of action revolves around the direct eradication of tumor cells. In our previous investigations, we formulated an oncolytic herpes simplex virus type 2 (OH2) and substantiated its anti-tumor efficacy both in vivo and in vitro. Subsequently, we embarked on a phase I/II clinical trial in China (NMPA, 2018L02743) and the USA (FDA, IND 27137) to assess OH2's safety, biodistribution, and anti-tumor activity as a standalone agent in patients with advanced solid tumors. In this investigation, our primary focus was to comprehend the influence of the major capsid protein VP5 of OH2 on its efficacy as an antitumor agent. Our findings underscore that the VP5 protein significantly amplifies OH2's oncolytic impact on A549 cells. Additionally, we observed that VP5 actively promotes the induction of apoptosis in A549 cells, both in vivo and in vitro. Through comprehensive transcriptional sequencing, we further authenticated that the VP5 protein triggers apoptosis-related signaling pathways and Gene Ontology (GO) terms in A549 cells. Moreover, we scrutinized differentially expressed genes in the p53-dependent apoptosis pathway and conducted meticulous in vitro validation of these genes. Subsequently, we delved deeper into unraveling the functional significance of the TP53I3 gene and conclusively affirmed that the VP5 protein induces apoptosis in A549 cells through the TP53I3 gene. These revelations illuminate the underlying mechanisms of OH2's antitumor activity and underscore the pivotal role played by the VP5 protein. The outcomes of our study harbor promising implications for the formulation of effective oncolytic virotherapy strategies in cancer treatment.

Significance of Pre-Treatment CALLY Score Combined with EBV-DNA Levels for Prognostication in Non-Metastatic Nasopharyngeal Cancer Patients: A Clinical Perspective.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models. Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis. Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort. Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.

Coagulation/co-catalytic membrane integrated system for fouling-resistant and efficient water purification.

Low-pressure catalytic membranes allow efficient rejection of particulates and simultaneously removing organics pollutant in water, but the accumulation of dissolved organic matters (DOM) on membrane surface, which cover the catalytic sites and cause membrane fouling, challenges their stable operation in practical wastewater treatment. Here we propose a ferric salt-based coagulation/co-catalytic membrane integrated system that can effectively mitigate the detrimental effects of DOM. Ferric salt (Fe3+) serving both as a DOM coagulant to lower the membrane fouling and as a co-catalyst with the membrane-embedded MoS2 nanosheets to drive perxymonosulfate (PMS) activation and pollutant degradation. The membrane functionalized with 2H-phased MoS2 nanosheets showed improved hydrophilicity and fouling resistance relative to the blank polysulfone membrane. Attributed to the DOM coagulation and co-catalytic generation of surface-bound radicals for decontamination at membrane surface, the catalytic membrane/PMS/ Fe3+ system showed much less membrane fouling and 2.6 times higher pollutant degradation rate in wastewater treatment than the catalytic membrane alone. Our work imply a great potential of coagulation/co-catalytic membrane integrated system for water purification application.