Glycogen synthase kinase-3: A potential immunotherapeutic target in tumor microenvironment.

Glycogen synthase kinase-3(GSK-3) is a protein kinase that can phosphorylate over a hundred substrates and regulate cell differentiation, proliferation, and death. Researchers have acknowledged the pivotal role of abnormal activation of GSK-3 in the progression of various diseases over the past few decades. Recent studies have mostly concentrated on investigating the function of GSK-3 in the tumor microenvironment, specifically examining the interaction between TAM, NK cells, B cells, and T cells. Furthermore, GSK-3 exhibits a strong association with immunological checkpoints, such as programmed cell death protein 1. Novel GSK-3 inhibitors have potential in tumor immunotherapy, exerting beneficial effects on hematologic diseases and solid tumors. Nevertheless, there is a lack of reviews about the correlation between tumor-associated immune cells and GSK-3. This study intends to analyze the function and mechanism of GSK-3 comprehensively and systematically in the tumor microenvironment, with a special focus on its influence on various immune cells. The objective is to present novel perspectives for GSK-3 immunotherapy.

Highly Robust Room-Temperature Interfacial Ferromagnetism in Ultrathin Co2Si Nanoplates.

The reduced dimensionality and interfacial effects in magnetic nanostructures open the feasibility to tailor magnetic ordering. Here, we report the synthesis of ultrathin metallic Co2Si nanoplates with a total thickness that is tunable to 2.2 nm. The interfacial magnetism coupled with the highly anisotropic nanoplate geometry leads to strong perpendicular magnetic anisotropy and robust hard ferromagnetism at room temperature, with a Curie temperature (TC) exceeding 950 K and a coercive field (HC) > 4.0 T at 3 K and 8750 Oe at 300 K. Theoretical calculations suggest that ferromagnetism originates from symmetry breaking and undercoordinated Co atoms at the Co2Si and SiO2 interface. With protection by the self-limiting intrinsic oxide, the interfacial ferromagnetism of the Co2Si nanoplates exhibits excellent environmental stability. The controllable growth of ambient stable Co2Si nanoplates as 2D hard ferromagnets could open exciting opportunities for fundamental studies and applications in Si-based spintronic devices.

Influenza and COVID-19 co-infection and vaccine effectiveness against severe cases: a mathematical modeling study.

Background: Influenza A virus have a distinctive ability to exacerbate SARS-CoV-2 infection proven by in vitro studies. Furthermore, clinical evidence suggests that co-infection with COVID-19 and influenza not only increases mortality but also prolongs the hospitalization of patients. COVID-19 is in a small-scale recurrent epidemic, increasing the likelihood of co-epidemic with seasonal influenza. The impact of co-infection with influenza virus and SARS-CoV-2 on the population remains unstudied. Method: Here, we developed an age-specific compartmental model to simulate the co-circulation of COVID-19 and influenza and estimate the number of co-infected patients under different scenarios of prevalent virus type and vaccine coverage. To decrease the risk of the population developing severity, we investigated the minimum coverage required for the COVID-19 vaccine in conjunction with the influenza vaccine, particularly during co-epidemic seasons. Result: Compared to the single epidemic, the transmission of the SARS-CoV-2 exhibits a lower trend and a delayed peak when co-epidemic with influenza. Number of co-infection cases is higher when SARS-CoV-2 co-epidemic with Influenza A virus than that with Influenza B virus. The number of co-infected cases increases as SARS-CoV-2 becomes more transmissible. As the proportion of individuals vaccinated with the COVID-19 vaccine and influenza vaccines increases, the peak number of co-infected severe illnesses and the number of severe illness cases decreases and the peak time is delayed, especially for those >60 years old. Conclusion: To minimize the number of severe illnesses arising from co-infection of influenza and COVID-19, in conjunction vaccinations in the population are important, especially priority for the elderly.

Seroprevalence of Avian Influenza A(H5N6) Virus Infection, Guangdong Province, China, 2022.

In 2022, we assessed avian influenza A virus subtype H5N6 seroprevalence among the general population in Guangdong Province, China, amid rising numbers of human infections. Among the tested samples, we found 1 to be seropositive, suggesting that the virus poses a low but present risk to the general population.

Safety and efficacy of onradivir in adults with acute uncomplicated influenza A infection: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Onradivir (ZSP1273) is a novel anti-influenza A virus inhibitor. Preclinical studies show that onradivir can inhibit influenza A H1N1 and H3N2 replication and increase the survival rate of infected animals. In this study, we aimed to evaluate the safety and efficacy of three onradivir dosing regimens versus placebo in outpatients with acute uncomplicated influenza A virus infection. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial at 20 clinical sites in China. Eligible participants were adults (18-65 years) with an influenza-like illness screened by rapid antigen testing at the first clinical visit, had the presence of a fever (axillary temperature ≥38·0°C), and had the presence of at least one moderate systemic and one respiratory symptom within 48 h of symptom onset. Patients were excluded if they were pregnant, allergic to onradivir, or had received any influenza antiviral medication within 7 days before enrolment. Participants were randomly assigned (1:1:1:1) into four groups by an interactive web response system: onradivir 200 mg twice per day group, onradivir 400 mg twice per day group, onradivir 600 mg once per day group, and a matching placebo group. A 5-day oral treatment course was initiated within 48 h after symptoms onset. The primary outcome was the time to alleviate influenza symptoms in the modified intention-to-treat population. Safety was a secondary outcome. We evaluated the patients' self-assessed severity of seven influenza symptoms on a 4-point ordinal scale, and the treatment-emergent adverse events in all patients. This trial is registered with ClinicalTrials.gov, number NCT04024137. FINDINGS: Between Dec 7, 2019, and May 18, 2020, a total of 205 patients were screened; of whom, 172 (84%) were randomly assigned to receive onradivir (n=43 in the 200 mg twice per day group; n=43 in the 400 mg twice per day group; and n=43 in the 600 mg once per day group), or placebo (n=42). Median age was 22 years (IQR 20-26). All three onradivir groups showed decreased median time to alleviate influenza symptoms (46·92 h [IQR 24·00-81·38] in the 200 mg twice per day group, 54·87 h [23·67-110·62] in the 400 mg twice per day group, and 40·05 h [17·70-65·82] in the 600 mg once per day) compared with the placebo group (62·87 h [36·40-113·25]). The median difference between the onradivir 600 mg once per day group and the placebo group was -22·82 h (p=0·0330). The most frequently reported treatment-emergent adverse event was diarrhoea (71 [42%] of 171), ranging from 33-65% of the patients in onradivir-treated groups compared with 10% in the placebo group; no serious adverse events were observed. INTERPRETATION: Onradivir showed a safety profile comparable to placebo, as well as higher efficacy than placebo in ameliorating influenza symptoms and lowering the viral load in adult patients with uncomplicated influenza infection, especially the onradivir 600 mg once per day regimen. FUNDING: National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, National Natural Science Foundation of China, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project, Emergency Key Program of Guangzhou Laboratory, Macao Science and Technology Development Fund, and Guangdong Raynovent Biotech.

In Situ Synthesis of Gold Nanoparticles from Chitin Nanogels and Their Drug Release Response to Stimulation.

In this study, gold nanoparticles (AuNPs) were synthesized in situ using chitin nanogels (CNGs) as templates to prepare composites (CNGs@AuNPs) with good photothermal properties, wherein their drug release properties in response to stimulation by near-infrared (NIR) light were investigated. AuNPs with particle sizes ranging from 2.5 nm to 90 nm were prepared by varying the reaction temperature and chloroauric acid concentration. The photothermal effect of different materials was probed by near-infrared light. Under 1 mg/mL of chloroauric acid at 120 °C, the prepared CNGs@AuNPs could increase the temperature by 32 °C within 10 min at a power of 2 W/cm2. The Adriamycin hydrochloride (DOX) was loaded into the CNGs@AuNPs to investigate their release behaviors under different pH values, temperatures, and near-infrared light stimulations. The results showed that CNGs@AuNPs were pH- and temperature-responsive, suggesting that low pH and high temperature could promote drug release. In addition, NIR light stimulation accelerated the drug release. Cellular experiments confirmed the synergistic effect of DOX-loaded CNGs@AuNPs on chemotherapy and photothermal therapy under NIR radiation.

Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial.

Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Low Temperature Synthesis of 2D p-Type α-In2 Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2 /Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2 Te3  nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2 /Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2 Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2 Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1  s-1 , and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2 Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2 Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Butterfly-tie like MnCO3@Mn3O4 heterostructure enhanced the electrochemical performances of aqueous zinc ion batteries.

Due to the limited exploitation and utilization of fossil energy resources in recent years, it is imperative to explore and develop new energy materials. As an electrode material for batteries, MnCO3 has the advantages of safety, non-toxicity, and wide availability of raw materials. But it also has some disadvantages, such as short cycle period and low conductivity. In order to improve these deficiencies, we designed a MnCO3@Mn3O4 heterostructure material by a simple solvothermal method, which possessed a microstructure of "butterfly-tie". Owing to the introduction of Mn3O4 and the layered structure of "butterfly-tie", MnCO3@Mn3O4 possessed a discharge capacity of 165 mAh/g when the current density was 0.2 A/g and exhibited satisfactory rate performance. The MnCO3@Mn3O4 heterostructure was optimized by density functional theory (DFT), and the deformation charge density was calculated. It was found that the MnCO3@Mn3O4 heterostructure is stable owing to the molecular interaction between the O atoms from MnCO3 and the Mn atoms from Mn3O4 at the interface of heterojunction. Therefore, the MnCO3@Mn3O4 heterostructure material has promising applications as safe and efficient cathode material for energy batteries.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Differentiate Clinical Characteristics Between Viral Pneumonia and Mycoplasma pneumoniae and Nomograms for Predicting Mycoplasma pneumoniae : A Retrospective Study in Primary Hospitals.

OBJECTIVE: To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary hospitals with the insufficient pathogen detection capacity. METHODS: We retrospectively reviewed the medical records of hospitalized children with acute respiratory tract infections, and pathogenic microbes test results were analyzed. Clinical characteristics, routine blood parameters and hospitalization duration and fee were compared between M. pneumoniae and viral pneumonia. We used in the multivariable logistic regression to predict the probability of children with M. pneumoniae and graphically represented by a dynamic nomogram. The discrimination and clinical utility of the model were confirmed by receiver operating characteristic and decision curve analysis curves. RESULT: A total of 375 children with community-acquired pneumonia were included. Mycoplasma infection accounted for the largest proportion (22.13%). The incidence of both hypothermia and vomiting was lower in M. pneumoniae compared to viral pneumonia (hypothermia: 10.50% vs. 0.00%; vomiting: 7.90% vs. 0.00%). The prevalence of hyperthermia was higher in M. pneumoniae (hyperthermia: 89.5% vs. 100%). Procalcitonin, peripheral blood white blood cell count and lymphocyte levels were higher in the viral pneumonia group, and eosinophil levels were conversely lower. As for the duration of illness, the mean length of stay was 5.20 ± 2.12 (viral pneumonia) and 6.27 ± 2.48 days ( M. pneumoniae ). Children with M. pneumoniae had higher overall hospital costs and required more medical treatment. The above were all statistically significant with a P < 0.05. The scoring system was established based on the above results. Receiver operating characteristic curves showed good model-discrimination ability with 0.844 of the area under the curve in the training set and 0.778 in the test set. Decision curve analysis curves demonstrated the discriminative superiority of this model. The web-based dynamic nomogram calculator is accessible at https://zhxylxy0160128.shinyapps.io/Nomogram/ . CONCLUSION: Nomograms have satisfactory discrimination, and clinical utility may benefit in predicting the probability of developing M. pneumoniae in children. Children with M. pneumoniae have a higher burden than those with viral pneumonia and may require more intensive in-hospital monitoring.

Degradation of Levofloxacin by a green zero-valent iron-loaded carbon composite activating peroxydisulfate system: Reactivity, products and mechanism.

In this study, a green zero-valent iron-loaded carbon composite (ZVI-SCG) was synthesized using coffee grounds and FeCl3 solution through two-steps method, and the synthesized ZVI-SCG was used in the activation of peroxydisulfate (PDS) to degrade Levofloxacin (LEX). Results revealed that ZVI-SCG exhibited a great potential for LEX removal by adsorption and catalytic degradation in the ZVI-SCG/PDS system, and 99% of LEX was removed in the ZVI-SCG/PDS system within 60 min. ZVI-SCG/PDS system showed a high reactivity toward LEX degradation under realistic environmental conditions. Also, the ZVI-SCG/PDS system could effectively degrade several quinolone antibiotics including gatifloxacin, ciprofloxacin and LEX in single and simultaneous removal modes. A potential reaction mechanism of LEX degradation by ZVI-SCG/PDS system was proposed, SO4•-, HO•, O2•- and 1O2 involved in radical and non-radical pathways took part in catalytic degradation of LEX by ZVI-SCG/PDS system, but HO• might be the main reactive species for LEX degradation. The possible degradation pathway of LEX was also proposed based on the identified ten intermediate products, LEX degradation was successfully achieved through decarboxylation, opening ring and hydroxylation processes. The potential toxicity of LEX and its oxidation products decreased significantly after treatment. This study provides a promising strategy of water treatment for the antibiotics-containing wastewater.

Preparation of Thin Film Composite (TFC) Membrane with DESPs Interlayer and Its Forward Osmosis (FO) Performance for Organic Solvent Recovery.

To explore the application of forward osmosis (FO) technology in the organic solvent recovery field, we prepared a new solvent-resistant triple layer thin film composite (TFC) membrane on the PI (polyimide) substrate. The deep eutectic supramolecular polymers (DESPs) interlayer was constructed on the substrate to improve the separation performance and solvent resistance. DESPs interlayer was formed by mixing and heating with cyclodextrin as the hydrogen bond acceptor and L-malic acid as the hydrogen bond donor. The chemical changes, surface property and morphology of the composite membrane with DESPs interlayer were characterized. The separation performance and stability of the triple layer composite membrane in organic solvent FO were studied. For the monascorubrin-ethanol system, the permeation flux of TFC/DESPs5-PI membrane could reach 9.51 LMH while the rejection rate of monascorubrin was 98.4% (1.0 M LiCl/ethanol as draw solution), which was better than the pristine membrane. Therefore, this solvent-resistant triple layer composite FO membrane has good potential for the recovery of organic solvents.

Inflammation-related indicators have a potential to increase overall quality of the prostate cancer management: a narrative review.

Background and Objective: Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The levels of inflammation-related indicators are correlated with prognosis across a wide variety of tumor types, including prostate cancer (PCa), but its diagnostic and prognostic value in PCa remains controversial. In the present review, the diagnostic and prognostic value of inflammation-related indicators in PCa patients is investigated. Methods: A literature review was performed using the PubMed database, screening articles from English and Chinese journals published mainly from 2015 to 2022. Key Content and Findings: Inflammation-related indicators based on haematological tests have some diagnostic and prognostic value not only when used alone but also in combination with common clinical indicators such as prostate-specific antigen (PSA), and can significantly improve the accuracy of diagnostic results. Elevated neutrophil-to-lymphocyte-count ratio (NLR) is strongly associated with the detection of PCa in men with PSA levels of 4-10 ng/mL. Preoperative NLR levels in localized PCa patients affect their overall survival (OS), cancer-specific survival (CSS), and biochemical recurrence-free survival (BCRFS) after radical prostatectomy (RP). In patients with castration-resistant prostate cancer (CRPC), a high NLR is associated with poorer OS, progression-free survival (PFS), CSS, and radiographic PFS. Platelet-to-lymphocyte-count ratio (PLR) appears to have the greatest accuracy in predicting an initial diagnosis of clinically significant PCa. The PLR also has the potential to predict the Gleason score. Patients with higher PLR levels have a higher risk of death compared to those with a lower PLR. Elevated procalcitonin (PCT) is correlated with the development of PCa and may be useful in improving the diagnostic accuracy of PCa. Elevated C-reactive protein (CRP) levels are an independent predictor of poorer OS in metastatic PCa. Conclusions: Numerous studies have been conducted on the value of inflammation-related indicators in guiding the diagnosis and treatment of PCa. The value of inflammation-related indicators in predicting the diagnosis and prognosis of PCa patients is now becoming clear.

A multifunctional metal-organic framework nanosystem disrupts redox homeostasis for synergistic therapy.

Synergistic therapies of photodynamic therapy (PDT) and chemodynamic therapy (CDT) via metal-organic frameworks (MOF) for cancer treatment have recently attracted a lot of attentions because of the limitations of insufficient reactive oxygen species (ROS) in single-modality approaches. However, few studies explored on the use of increased ROS synergized with chemotherapy (CT) to address the issue of inadequate anti-tumor efficacy in single-modality regimens. Here, the desired cascade nanoplatforms (noted as MOF(Cu)@Dox-PL NPs) were fabricated by a solvothermal method using tetrakis (4-carboxyphenyl) porphyrin (TCPP) and zirconyl(di)chloride octahydrate (ZrOCl2·8H2O) as raw material, followed by Cu2+ introduced into the porphyrin ring and doxorubicin (DOX) loaded into the nanoframework. In addition, the nanoparticles (NPs) were electrostatically and hydrophobically coated with phospholipid (PL) to improve the biocompatibility of the nanosystems. Singlet oxygen (1O2) was created by the MOF(Cu)@Dox-PL NPs to disturb intracellular redox equilibrium. The acidic microenvironment in cancer cells may cause the prior release of DOX, which encourages the production of hydrogen peroxide (H2O2). And the doped Cu2+ could deplete overexpressed reduced glutathione (GSH) to produce hydroxyl radicals (·OH) by catalyzing H2O2, further causing redox dyshomeostasis. In vivo experiments revealed that MOF(Cu)@Dox-PL nanosystem possessed good biosafety and a compelling therapeutic effect in 4T1 tumor-bearing mice. As a novel nanosystem, MOF(Cu)@Dox-PL NPs showed great potential in synergistic therapy based on redox dyshomeostasis for improving anti-tumor efficacy with high specificity.

Real-time assessment of COVID-19 epidemic in Guangdong Province, China using mathematical models.

China government has relaxed the response measures of COVID-19 in early December 2022. In this report, we assessed the number of infections, the number of severe cases based on the current epidemic trend (October 22, 2022 to November 30, 2022) using a transmission dynamics model, called modified susceptible-exposed-infectious-removed (SEIR) to provide valuable information to ensure the medical operation of the healthcare system under the new situation. Our model showed that the present outbreak in Guangdong Province peaked during December 21, 2022 to December 25, 2022 with about 14.98 million new infections (95% CI: 14.23-15.73 million). The cumulative number of infections will reach about 70% of the province's population from December 24, 2022 to December 26, 2022. The number of existing severe cases is expected to peak during January 1, 2023 to January 5, 2023 with a peak number of approximately 101.45 thousand (95% CI: 96.38-106.52 thousand). In addition, the epidemic in Guangzhou which is the capital city of Guangdong Province is expected to have peaked around December 22, 2022 to December 23, 2022 with the number of new infections at the peak being about 2.45 million (95% CI: 2.33-2.57 million). The cumulative number of infected people will reach about 70% of the city's population from December 24, 2022 to December 25, 2022 and the number of existing severe cases is expected to peak around January 4, 2023 to January 6, 2023 with the number of existing severe cases at the peak being about 6.32 thousand (95% CI: 6.00-6.64 thousand). Predicted results enable the government to prepare medically and plan for potential risks in advance.

Critical review on quality of methodology and recommendations of clinical practice guidelines for peri-implantitis.

BACKGROUND: Peri-implantitis is of high prevalence with the popularity of dental implants nowadays. Guidelines or consensus have been developed in succession, and we are little-known about their quality. The objective of this study is to evaluate the methodological quality of these guidelines and analyze the consistency of the clinical recommendations. METHODS: We searched for guidelines or consensus on prevention, diagnosis, and/or treatment of peri-implantitis through PubMed, Web of Science, Cochrane Library until January 15th, 2022. In addition, we also searched the websites of the American Dental Association, International Team for Implantology, FDI World Dental Federation, and some guideline collection databases. Appraisal of Guidelines for Research & Evaluation II methodological quality instrument was used to assess the selected guidelines. Furthermore, we described the consistency of recommendations across the included guidelines. RESULTS: In total, 15 guidelines were included. The mean values of the six domains score all below 50%. The mean scores of Applicability were lowest (mean:15%, range:4-29%). As to the overall quality, eleven (73%) were recommended after being modified, and four (27%) were not recommended. Among the clinical recommendations, 53 (67.09%) are for treatment of peri-implantitis, 13 (16.46%) for monitoring issue, 7 (8.86%) for diagnosis, 3 (3.80%) for the disease prevention. CONCLUSIONS: Improving methodology quality and strengthening clinical evidence is essential in the future guideline development in a range of disciplines for improving the treatment effectiveness of people with peri-implantitis. And there is a lack of integrated guidelines in the case of the COVID-19 pandemic.

Extracellular vesicles from bone marrow mesenchymal stem cells alleviate acute rejection injury after liver transplantation by carrying miR-22-3p and inducing M2 polarization of Kupffer cells.

BACKGROUND: Acute rejection (AR) is a major problem following liver transplantation. Extracellular vesicles (EVs) are involved in various pathological processes including liver disease. The present study investigated the effect of EVs derived from bone marrow mesenchymal stem cells (BMSCs) on AR injury after orthotopic liver transplantation (OLT) in mice. METHODS: BMSCs and EVs were isolated and identified. The OLT mouse model was established using Kamada's two-cuff method and injection with EVs, followed by liver function detection and measurement of inflammatory cytokines (interleukin-10, interferon-γ, and tumor necrosis factor-α), M1 and M2 markers (tumor necrosis factor-α, inducible nitric oxide synthase, resistin like alpha, and Arg1) were detected. Kupffer cells (KCs) were cultured and treated with lipopolysaccharides. miR-22-3p expression was detected. The effect of EVs-shuttled miR-22-3p on Kupffer cell polarization was studied. Binding relation of miR-22-3p and interferon regulatory factor 8 (IRF8) was verified. The effect of IRF8 on KC polarization was verified. RESULTS: BMSC-EV treatment enhanced liver function of OLT mice and alleviated AR and apoptosis, which were annulled after removing KCs. EVs induced KC M2 polarization. Mechanically, EVs carried miR-22-3p into KCs, upregulated miR-22-3p in KCs, and inhibited IRF8 expression. Upregulation of IRF8 in KCs inhibited EV-induced KC M2 polarization. CONCLUSIONS: BMSCs-EVs carry miR-22-3p into KCs and upregulate miR-22-3p, inhibit IRF8 expression, induce KC M2 polarization, and attenuate AR injury after liver transplantation.