An Osteoimmunomodulatory Biopatch Potentiates Stem Cell Therapies for Bone Regeneration by Simultaneously Regulating IL-17/Ferroptosis Signaling Pathways.

Currently, there are still great challenges in promoting bone defect healing, a common health problem affecting millions of people. Herein an osteoimmunity-regulating biopatch capable of promoting stem cell-based therapies for bone regeneration is developed. A totally biodegradable conjugate is first synthesized, which can self-assemble into bioactive nano micelles (PPT NMs). This nanotherapy effectively improves the osteogenesis of periodontal ligament stem cells (PDLSCs) under pathological conditions, by simultaneously regulating IL-17 signaling and ferroptosis pathways. Incorporation of PPT NMs into biodegradable electrospun nanofibers affords a bioactive patch, which notably improves bone formation in two rat bone defect models. A Janus bio patch is then engineered by integrating the bioactive patch with a stem cell sheet of PDLSCs. The obtained biopatch shows additionally potentiated bone regeneration capacity, by synergistically regulating osteoimmune microenvironment and facilitating stem cell differentiation. Further surface functionalization of the biopatch with tannic acid considerably increases its adhesion to the bone defect, prolongs local retention, and sustains bioactivities, thereby offering much better repair effects in rats with mandibular or cranial bone defects. Moreover, the engineered bioactive patches display good safety. Besides bone defects, this osteoimmunity-regulating biopatch strategy can be applied to promote stem cell therapies for spinal cord injury, wound healing, and skin burns.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Glycoengineering in antigen-specific immunotherapies.

Advances in immunotherapy have revolutionized modern medical care paradigms. However, many patients respond poorly to the current FDA-approved treatment regimens that primarily target protein-based antigens or checkpoints. Current progress in developing therapeutic strategies that target disease-associated glycans has pinpointed a new class of glycoimmune checkpoints that function orthogonally to the established protein-immune checkpoints. Glycoengineering using chemical, enzymatic, and genetic methods is also increasingly recognized for its massive potential to improve biopharmaceuticals, such as tailoring therapies with antigen-targeting agents. Here, we review the recent development and applications of glycoengineering of antibodies and cells to suit therapeutic applications. We highlight living-cell glycoengineering strategies on cancer and immune cells for better therapeutic efficacy against specific antigens by leveraging the pre-existing immune machinery or instructing de novo creation of targeting agents. We also discuss glycoengineering strategies for studying basic immuno-oncology. Collectively, glycoengineering has a significant contribution to the design of antigen-specific immunotherapies.

An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine.

Background: Hong Kong enforced stringent travel restrictions during the COVID-19 pandemic. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: Retrospective cohort study summarising the characteristics of imported cases detected in Hong Kong between 13 November 2020 and 31 January 2022, when compulsory quarantine was implemented. Findings: A total of 2269 imported COVID-19 cases aged 0-85 years were identified, of which 48.6 % detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than in ancestral strain and other variants cases (12 days; p < 0.001). Lower Ct values at isolation were observed in Omicron cases than in ancestral strain or other variants cases. No Omicron cases were detected beyond 14 days after arrival. Cases detected after 14 days of quarantine (n=58, 2.6 %) were more likely asymptomatic at isolation and had higher Ct value during isolation, some of them indicating re-positivity or post-arrival infections. Conclusions: Testing inbound travellers at arrival and during quarantine can detect imported cases early, but may not prevent all COVID-19 introductions into the community. Public health measures should be adapted in response to the emergence of SARS-CoV-2 variants based on evidence from ongoing surveillance.

Optimizing anaerobic digestion: Benefits of mild temperature transition from thermophilic to mesophilic conditions.

Anaerobic digestion (AD) plays a significant role in renewable energy recovery. Upgrading AD from thermophilic (50-57 °C) to mesophilic (30-38 °C) conditions to enhance process stability and reduce energy input remains challenging due to the high sensitivity of thermophilic microbiomes to temperature fluctuations. Here we compare the effects of two decreasing-temperature modes from 55 to 35 °C on cell viability, microbial dynamics, and interspecies interactions. A sharp transition (ST) is a one-step transition by 20 °C d-1, while a mild transition (MT) is a stepwise transition by 1 °C d-1. We find a greater decrease in methane production with ST (88.8%) compared to MT (38.9%) during the transition period. ST mode overproduced reactive oxygen species by 1.6-fold, increased membrane permeability by 2.2-fold, and downregulated microbial energy metabolism by 25.1%, leading to increased apoptosis of anaerobes by 1.9-fold and release of intracellular substances by 2.9-fold, further constraining methanogenesis. The higher (1.6 vs. 1.1 copies per gyrA) metabolic activity of acetate-dependent methanogenesis implied more efficient methane production in a steady mesophilic, MT-mediated system. Metagenomic binning and network analyses indicated that ST induced dysbiosis in keystone species and greatly enhanced microbial functional redundancy, causing loss of microbial syntrophic interactions and redundant metabolic pathways. In contrast, the greater microbial interconnections (average degrees 44.9 vs. 22.1) in MT at a steady mesophilic state suggested that MT could better maintain necessary system functionality and stability through microbial syntrophy or specialized pathways. Adopting MT to transform thermophilic digesters into mesophilic digesters is feasible and could potentially enhance the further optimization and broader application of practical anaerobic engineering.

Poor outcome in congenital mesoblastic nephroma with TPM3::NTRK1 fusion: a case report from multi-disciplinary treatment to molecular tumor board.

Background: Congenital mesoblastic nephroma (CMN) is a rare renal tumor with good prognosis in children; however, cellular CMN is a special subtype with poor prognosis. The ETV6 fusion gene has been found in some cellular CMNs, whereas CMNs with TPM3::NTRK1 fusion gene have not been reported. This study aims to share the progression and treatment of a case of CMNs with TPM3::NTRK1 fusion gene, in order to provide experience for the diagnosis and treatment of such specific diseases. Case Description: We report a case of CMN with TPM3::NTRK1 fusion gene and a 3-year course of disease that originated during the fetal period. The child experienced rapid tumor progression 22 months after birth, followed by tumor recurrence 3 months after complete resection of CMN. Although traditional chemotherapy could not prevent the tumor progression. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib resulted in significant inhibitory effects on metastatic lesions in the lungs, liver, and peritoneum. However, the patient ultimately died as the tumor became resistant to larotrectinib. Conclusions: CMN, is a rare pediatric renal tumor that warrant prompt surgical management. A watchful waiting approach may allow for aggressive growth of metastatic disease, as seen in this case of cellular CMN with TPM3::NTRK1 fusion gene, TRK inhibitors can play significant roles in the treatment of CMN with TPM3::NTRK1 fusion gene, but we still need to pay attention to the phenomenon of drug resistance to larotrectinib caused by site mutations of TRKA.

A critical review of comammox and synergistic nitrogen removal coupling anammox: Mechanisms and regulatory strategies.

Nitrification is highly crucial for both anammox systems and the global nitrogen cycle. The discovery of complete ammonia oxidation (comammox) challenges the inherent concept of nitrification as a two-step process. Its wide distribution, adaptability to low substrate environments, low sludge production, and low greenhouse gas emissions may make it a promising new nitrogen removal treatment process. Meanwhile, anammox technology is considered the most suitable process for future wastewater treatment. The diverse metabolic capabilities and similar ecological niches of comammox bacteria and anammox bacteria are expected to achieve synergistic nitrogen removal within a single system. However, previous studies have overlooked the existence of comammox, and it is necessary to re-evaluate the conclusions drawn. This paper outlined the ecophysiological characteristics of comammox bacteria and summarized the environmental factors affecting their growth. Furthermore, it focused on the enrichment, regulatory strategies, and nitrogen removal mechanisms of comammox and anammox, with a comparative analysis of hydroxylamine, a particular intermediate product. Overall, this is the first critical overview of the conclusions drawn from the last few years of research on comammox-anammox, highlighting possible next steps for research.

Erythroid-intrinsic activation of TLR8 impairs erythropoiesis in inherited anemia.

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Mechanisms underlying the therapeutic effects of Gang Huo Qing wen granules in the treatment of influenza based on network pharmacology, molecular docking and molecular dynamics.

Influenza (Flu) is a severe health, medical, and economic problem, but no medication that has excellent outcomes and lowers the occurrence of these problems is now available. GanghuoQingwenGranules (GHQWG) is a common Chinese herbal formula for the treatment of influenza (flu). However, its methods of action remain unknown. We used network pharmacology, molecular docking, and molecular dynamics simulation techniques to investigate the pharmacological mechanism of GHQWG in flu. TCMSP and various types of literature were used to obtain active molecules and targets of GHQWG. Flu-related targets were found in the Online Mendelian Inheritance in Man (OMIM) database, the DisFeNET database, the Therapeutic Target Database (TTD), and the DrugBank database. To screen the key targets, a protein-protein interaction (PPI) network was constructed. DAVID was used to analyze GO and KEGG pathway enrichment. Target tissue and organ distribution was assessed. Molecular docking was used to evaluate interactions between possible targets and active molecules. For the ideal core protein-compound complexes obtained using molecular docking, a molecular dynamics simulation was performed. In total, 90 active molecules and 312 GHQWG targets were discovered. The PPI network's topology highlighted six key targets. GHQWG's effects are mediated via genes involved in inflammation, apoptosis, and oxidative stress, as well as the TNF and IL-17 signaling pathways, according to GO and KEGG pathway enrichment analysis. Molecular docking and molecular dynamics simulations demonstrated that the active compounds and tested targets had strong binding capabilities. This analysis accurately predicts the effective components, possible targets, and pathways involved in GHQWG flu treatment. We proposed a novel study strategy for future studies on the molecular processes of GHQWG in flu treatment. Furthermore, the possible active components provide a dependable source for flu drug screening.

U(VI) sorption on illite in the Co-existence of carbonates and humic substances.

The presence of carbonates or humic substances (HS) will significantly affect the species and chemical behavior of U(VI) in solution, but lacking systematic exploration of the coupling effect of carbonates and HS under near real environmental conditions at present. Herein, the sorption behavior of U(VI) on illite was systematically studied in the co-existence of carbonates and HS including both humic acid (HA) and fulvic acid (FA) by batch technique. The distribution coefficients (Kd) increased as function of time and temperature but decreased with increasing concentrations of initial U(VI), Ca2+, and Mg2+, as well as ion strength. At pH 2.0-10.5, the Kd values first increased rapidly and then decreased visibly, with its maximum value appearing at pH 5.0, owning to the changes in the interaction between illite and the dominant species of U(VI) from electrostatic attraction to electrostatic repulsion. The sorption was a heterogeneous, spontaneous, and endothermic chemical process, which could be well described by pseudo-second-order kinetic and Flory-Huggins isotherm models. When carbonates and HA/FA coexisted, the Kd values always increased first and then decreased as a function of pH, with the only difference for HA and FA being the key pH (pHkey) at which the promoting and inhibiting effects on the sorption of U(VI) onto illite undergo a transition. The carbonates and HS have a synergistic inhibitory effect on the U(VI) sorption onto illite at pH 7.8. FTIR and XPS spectra demonstrated that the hydroxyl groups on the illite surface and in the HS were involved in U(VI) sorption on illite in the presence of carbonates. These results provide valuable data for a deeper understanding of U(VI) migration in geological media.

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Genetically Engineered Membrane-Coated Nanoparticles for Enhanced Prostate-Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration-Resistant Prostate Cancer.

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.

circRNA-0015004 act as a ceRNA to promote RCC2 expression in hepatocellular carcinoma.

Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.

A review of microplastics on anammox: Influences and mechanisms.

Microplastics (MPs) are prevalent in diverse environmental settings, posing a threat to plants and animals in the water and soil and even human health, and eventually converged in wastewater treatment plants (WWTPs), threatening the stable operation of anaerobic ammonium oxidation (anammox). Consequently, a comprehensive summary of their impacts on anammox and the underlying mechanisms must be provided. This article reviews the sources and removal efficiency of MPs in WWTPs, as well as the influencing factors and mechanisms on anammox systems. Numerous studies have demonstrated that MPs in the environment can enter WWTPs via domestic wastewater, rainwater, and industrial wastewater discharges. More than 90% of these MPs are found to accumulate in the sludge following their passage through the treatment units of the WWTPs, affecting the characteristics of the sludge and the efficiency of the microorganisms treating the wastewater. The key parameters of MPs, encompassing concentration, particle size, and type, exert a notable influence on the nitrogen removal efficiency, physicochemical characteristics of sludge, and microbial community structure in anammox systems. It is noteworthy that extracellular polymer secretion (EPS) and reactive oxygen stress (ROS) are important impact mechanisms by which MPs exposure affects anammox systems. In addition, the influence of MPs exposure on the microbial community structure of anammox cells represents a crucial mechanism that demands attention. Future research endeavors will delve into additional crucial parameters of MPs, such as shape and aging, to investigate their effects and mechanisms on anammox. Furthermore, the effective mitigation strategies will also be developed. The paper provides a fresh insight to reveal the influences of MPs exposure on the anammox process and its influence mechanisms, and lays the groundwork for further exploration into the influence of MPs on anammox and potential mitigation strategies.

Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong.

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission.

Medical Resource Management in Emergency Hierarchical Diagnosis and Treatment Systems: A Research Framework.

The occurrence of major public health crises, like the COVID-19 epidemic, present significant challenges to healthcare systems and the management of emergency medical resources worldwide. This study, by examining the practices of emergency medical resource management in select countries during the COVID-19 epidemic, and reviewing the relevant literature, finds that emergency hierarchical diagnosis and treatment systems (EHDTSs) play a crucial role in managing emergency resources effectively. To address key issues of emergency resource management in EHDTSs, we examine the features of EHDTSs and develop a research framework for emergency resource management in EHDTSs, especially focusing on the management of emergency medical personnel and medical supplies during evolving epidemics. The research framework identifies key issues of emergency medical resource management in EHDTSs, including the sharing and scheduling of emergency medical supplies, the establishment and sharing of emergency medical supply warehouses, and the integrated dispatch of emergency medical personnel. The proposed framework not only offers insights for future research but also can facilitate better emergency medical resource management in EHDTSs during major public health emergencies.

Evaluating the effectiveness of cytoreductive surgery in oligometastatic prostate cancer: insights from quantitative analysis and retrospective cohort studies.

BACKGROUND: Oligometastatic prostate cancer (OmPCa) is characterized by a restricted number of metastatic lesions confined to a limited organ range, presenting a distinct clinical challenge. The role of cytoreductive prostatectomy (CRP) in managing this specific metastatic stage has gained attention but remains controversial. This study aims to assess the effectiveness of CRP in OmPCa by synthesizing outcomes from previous studies and analyzing data from a multicenter, retrospective cohort. METHODS: We focused on evaluating overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and castration-resistant prostate cancer-free survival (CRPCFS) as primary outcomes. A multicenter comparative retrospective analysis was also conducted on OmPCa patients treated with CRP versus those receiving androgen deprivation therapy (ADT) alone from January 2008 to June 2018. We gathered and analyzed data on patient demographics, tumor characteristics, surgical outcomes, and survival metrics. RESULTS: The quantitative analysis included 18 studies(2 randomized controlled trial (RCT) and 16 non-RCT studies),comprising a total of 1733 patients with oligometastatic prostate cancer,this is the largest number of samples included in the same subject research at present.The pooled analysis demonstrated that cytoreductive surgery was associated with significantly improved OS (hazard ratio [HR]: 0.50, 95% confidence interval[CI]: 0.40-0.60) ,PFS (HR: 0.39, 95%[CI]: 0.27-0.51) ,CSS (HR: 0.44, 95%[CI]: 0.23-0.65) and CRPCFS (HR: 0.48, 95%[CI]: 0.36-0.59) compared to non-surgical management.In addition,OS ,PFS and CRPCFS showed better results in the CRP group in all analyses(RCT and non-RCT).Additionally,in our multicenter retrospective research analysis, 64 patients with oligometastatic prostate cancer were included ,32 underwent CRP (50%), and 32 underwent ADT alone (50%).The median follow-up time was 40.1 (18.9-51.3) months.The OS (P=0.0182), PFS (P=0.0297), and CRPCFS (P=0.0125) had statistical difference between the two matched cohorts.Moreover,we observed 8(25%) cases of perioperative complications, with the most common being urinary incontinence(9.4%). CONCLUSIONS: Incorporating CRP alongside ADT in the treatment protocol for OmPCa significantly enhances patient outcomes in terms of OS, PFS, and CRPC-free survival, underscoring the potential benefit of this surgical approach in the specified patient population.

Electrolyte Design Enables Rechargeable LiFePO4/Graphite Batteries from -80°C to 80°C.

Lithium iron phosphate (LFP)/graphite batteries have long dominated the energy storage battery market and are anticipated to become the dominant technology in the global power battery market. However, the poor fast-charging capability and low-temperature performance of LFP/graphite batteries seriously hinder their further spread. These limitations are strongly associated with the interfacial Li-ion transport. Here we report a wide-temperature-range ester-based electrolyte that exhibits high ionic conductivity, fast interfacial kinetics and excellent film-forming ability by regulating the anion chemistry of Li salt. The interfacial barrier of the battery is quantitatively unraveled by employing three-electrode system and distribution of relaxation time technique. The superior role of the proposed electrolyte in preventing Li0 plating and sustaining homogeneous and stable interphases are also systematically investigated. The LFP/graphite cells exhibit rechargeability in an ultrawide temperature range of -80°C to 80°C and outstanding fast-charging capability without compromising lifespan. Specially, the practical LFP/graphite pouch cells achieve 80.2% capacity retention after 1200 cycles (2 C) and 10-min charge to 89% (5 C) at 25°C and provides reliable power even at -80°C.

Cartilage decellularized matrix hydrogel loaded with protocatechualdehyde for targeted epiphycan treatment of osteoarthritis.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Spatial heterogeneity analysis for the transmission of syphilis disease in China via a data-validated reaction-diffusion model.

Based on the distinctive spatial diffusion characteristics observed in syphilis transmission patterns, this paper introduces a novel reaction-diffusion model for syphilis disease dynamics, incorporating general incidence functions within a heterogeneous environment. We derive the basic reproduction number essential for threshold dynamics and investigate the uniform persistence of the model. We validate the model and estimate its parameters by employing the multi-objective Markov Chain Monte Carlo (MCMC) method, using real syphilis data from the years 2004 to 2018 in China. Furthermore, we explore the impact of spatial heterogeneity and intervention measures on syphilis transmission. Our findings reveal several key insights: (1) In addition to the original high-incidence areas of syphilis, Xinjiang, Guizhou, Hunan and Northeast China have also emerged as high-incidence regions for syphilis in China. (2) The latent syphilis cases represent the highest proportion of newly reported cases, highlighting the critical importance of considering their role in transmission dynamics to avoid underestimation of syphilis outbreaks. (3) Neglecting spatial heterogeneity results in an underestimation of disease prevalence and the number of syphilis-infected individuals, undermining effective disease prevention and control strategies. (4) The initial conditions have minimal impact on the long-term spatial distribution of syphilis-infected individuals in scenarios of varying diffusion rates. This study underscores the significance of spatial dynamics and intervention measures in assessing and managing syphilis transmission, which offers insights for public health policymakers.