Functional UiO-66 for highly selective adsorption of N-nitrosodipropylamine: adsorption performance and mechanisms.

N-Nitrosodipropylamine (NDPA) is a class of nitrogenous disinfection by-products (N-DBPs) with high toxicity. Although NDPA present in water bodies is at relatively low concentrations, the potential risk is high due to its high toxicity and bioaccumulation. Metal-organic frameworks (MOFs), a new type of porous material with remarkable functionality, have shown great performance in a wide variety of applications in adsorption. This is the first study investigating the adsorption of MOFs on NDPA. Herein, UiO-66 with -NH2 and imidazolium functional groups were synthesized by modifying UiO-66 after amination. Adsorption kinetics and isotherm models were used to compare the adsorption properties of the two materials for low-concentration NDPA in water. The results showed that the behavior of all the adsorbents was consistent with the Langmuir model and the pseudo-second-order model and that the adsorption was homogeneous chemisorption. The structures of the nanoparticles were characterized by FTIR, zeta potential, XRD, SEM and BET measurements. Based on the characteristics, four adsorption mechanisms, namely electron conjugation, coordination reaction, anion-π interaction, and van der Waals forces, were simultaneously involved in the adsorption. The influencing factor experiment revealed that the adsorption of UiO-66-NH2 and (I-)Meim-UiO-66 involved hydrogen bonding and electrostatic interactions, respectively.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy.

AIM: To observe the therapeutic effect of conbercept on diabetic macular edema (DME) complicated with diabetic nephropathy (DN). METHODS: In this retrospective study, 54 patients (54 eyes) that diagnosed as DME from January 2017 to October 2021 were collected. The patients were divided into two groups: DME patients with DN (25 eyes), and DME patients without DN (29 eyes). General conditions were collected before treatment, laboratory tests include fasting blood glucose, HbA1c, microalbumin/creatinine, serum creatinine. Optical coherence tomography (OCT) was used to check the ellipsoidal zone (EZ) and external limiting membrane (ELM) integrity. Central macular thickness (CMT), best corrected visual acuity (BCVA), and retinal hyperreflective foci (HF) as well as numbers of injections were recorded. RESULTS: There were significant differences between fasting blood glucose, HbA1c, serum creatinine, urinary microalbumin/creatinine, and estimated glomerular filtration rate (eGFR) between the two groups (all P<0.05). EZ and ELM continuity in the DME+DN group was worse than that in the DME group (P<0.05). BCVA (logMAR) in the DME group was significantly better than that in the DME+DN group at the same time points during treatment (all P<0.05). CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points (all P<0.05) and significantly decreased in both groups with time during treatment. At 6mo after treatment, the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86, respectively. CONCLUSION: Conbercept has a significant effect in short-term treatment of DME patients with or without DN, and can significantly ameliorate BCVA, CMT and the number of HF, treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Resistance training combined with ß-hydroxy ß-methylbutyrate for patients with critical illness: A four-arm, mixed-methods, feasibility randomised controlled trial.

OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.

Deep evolutionary fusion neural network: a new prediction standard for infectious disease incidence rates.

BACKGROUND: Previously, many methods have been used to predict the incidence trends of infectious diseases. There are numerous methods for predicting the incidence trends of infectious diseases, and they have exhibited varying degrees of success. However, there are a lack of prediction benchmarks that integrate linear and nonlinear methods and effectively use internet data. The aim of this paper is to develop a prediction model of the incidence rate of infectious diseases that integrates multiple methods and multisource data, realizing ground-breaking research. RESULTS: The infectious disease dataset is from an official release and includes four national and three regional datasets. The Baidu index platform provides internet data. We choose a single model (seasonal autoregressive integrated moving average (SARIMA), nonlinear autoregressive neural network (NAR), and long short-term memory (LSTM)) and a deep evolutionary fusion neural network (DEFNN). The DEFNN is built using the idea of neural evolution and fusion, and the DEFNN + is built using multisource data. We compare the model accuracy on reference group data and validate the model generalizability on external data. (1) The loss of SA-LSTM in the reference group dataset is 0.4919, which is significantly better than that of other single models. (2) The loss values of SA-LSTM on the national and regional external datasets are 0.9666, 1.2437, 0.2472, 0.7239, 1.4026, and 0.6868. (3) When multisource indices are added to the national dataset, the loss of the DEFNN + increases to 0.4212, 0.8218, 1.0331, and 0.8575. CONCLUSIONS: We propose an SA-LSTM optimization model with good accuracy and generalizability based on the concept of multiple methods and multiple data fusion. DEFNN enriches and supplements infectious disease prediction methodologies, can serve as a new benchmark for future infectious disease predictions and provides a reference for the prediction of the incidence rates of various infectious diseases.

Identification of associated risk factors for serological distribution of hepatitis B virus via machine learning models.

BACKGROUND: The provincial-level sero-survey was launched to learn the updated seroprevalence of hepatitis B virus (HBV) infection in the general population aged 1-69 years in Chongqing and to assess the risk factors for HBV infection to effectively screen persons with chronic hepatitis B (CHB). METHODS: A total of 1828 individuals aged 1-69 years were investigated, and hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), and antibody to B core antigen (HBcAb) were detected. Logistic regression and three machine learning (ML) algorithms, including random forest (RF), support vector machine (SVM), and stochastic gradient boosting (SGB), were developed for analysis. RESULTS: The HBsAg prevalence of the total population was 3.83%, and among persons aged 1-14 years and 15-69 years, it was 0.24% and 4.89%, respectively. A large figure of 95.18% (770/809) of adults was unaware of their occult HBV infection. Age, region, and immunization history were found to be statistically associated with HBcAb prevalence with a logistic regression model. The prediction accuracies were 0.717, 0.727, and 0.725 for the proposed RF, SVM, and SGB models, respectively. CONCLUSIONS: The logistic regression integrated with ML models could helpfully screen the risk factors for HBV infection and identify high-risk populations with CHB.

A trinary support of Ni/NiO/C to immobilize Ir nanoclusters for alkaline hydrogen oxidation.

The hydrogen oxidation reaction is an important process in anion exchange membrane fuel cells with alkaline solutions. The pursuit of efficient catalysts for alkaline hydrogen oxidation has attracted considerable attention. In this study, we present a precursor route for the synthesis of a new Ir-based catalyst (Ir-Ni/NiO/C), in which Ir nanoclusters were immobilized on the generated Ni/NiO/C support derived from a metal-organic framework. The small size of Ir clusters facilitates the exposure of catalytically active sites. The electronic interplay between the Ir nanoclusters and the Ni/NiO/C support optimized the hydrogen binding energy (HBE) and hydroxide binding energy (OHBE) on the surface, which is unattainable on the contrasting Ir-C, Ir-Ni/C, and Ir-NiO/C products. The optimized catalyst shows excellent mass activity for alkaline hydrogen oxidation, which is 3.1 times that of the Pt/C catalyst. This study presents a promising pathway for the development of advanced HOR catalysts.

Iodine status of school-aged children in the changing context of universal salt iodization program during 1997-2018 in Chongqing, China.

OBJECTIVE: To illustrate the changes of iodized salt usage, goiter rate of school-aged children and median urinary iodine concentration (MUIC) of school-aged children in Chongqing for the last 21 years. This study aims to estimate the variational provincial status of iodine nutrition and provide scientific evidence for fine-tuning and adaptation of the current program. METHODS: Different number of families and school children aged 8-10 years from Chongqing during 1997-2018 participated in the study. UIC and iodine content in table salt were measured. Thyroid volumes of students were examined and goiter prevalence was calculated across years. RESULTS: The median iodine content of table salt was negatively associated with years(r = -0.727, P < 0.01). The MUIC were decreased annually (ranged between 200 and 300 µg/L) and was negatively associated with year(r = -0.831, P < 0.01). Goiter of school-aged children in Chongqing was decreased from the highest rate of 23.58% in 1999 to 1.62% in 2018(Cochran-Armitage Trend Test: χ2=-30.695, P < 0.01). Thyroid volume were negatively associated with years(r = -0.962, P < 0.01) and had a positive relationship with MUIC 1997-2018 (r = 0.862, P < 0.01). CONCLUSIONS: The consumption of adequately iodized salt can eliminate Iodine deficiency disorders (IDD) in children, but possible excessive iodine intake from salt could result in high urinary iodine excretion and even goiter. A systematic, well-designed and continual program monitoring is essential to ensure the adequacy of iodine fortification levels and to regularly change the iodine concentration in household table salt.

Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

Trade-offs inside the black box of neoantigen prediction.

Success of precision neoantigen-based immunotherapies hinges on the selection of immunogenic neoantigens, yet currently neither large-scale datasets nor streamlined methods are available to achieve this goal. Müller et al. present a large experimental dataset resource along with machine learning-based models to classify immunogenic neoantigens.

Biomechanical Analysis of Titanium Dental Implants in the All-on-4 Treatment with Different Implant-Abutment Connections: A Three-Dimensional Finite Element Study.

The type of implant-abutment connection is one of the factors influencing the distribution of occlusal forces. This study aims to investigate the biomechanical performance of the mandibular all-on-4 treatment with different implant-abutment connections. Two connection types with 30° abutments and 18-mm implant fixtures were chosen for the posterior implants of the all-on-4 assembly. For the external hexagon connection (EHC) group, the implants with 4 mm in diameter were used. For the internal hexagon connection (IHC) group, we selected implants with 4.3 mm in diameter. A vertical force of 190 N was applied to the cantilever region. The FEA results indicated that the most stressed region in the two groups was prosthetic screws, followed by multi-unit abutments (MUAs). The lowest values of von Mises stress were both observed on the bone. The peak stress value of the implant screw and implant fixture in the EHC group were 37.75% and 33.03% lower than the IHC group, respectively. For stress distribution patterns, the load force tended to be concentrated at locations where components were interconnected. The EHC and IHC are clinically durable under the tested loading conditions, but the prosthetic screws and MUAs can be the weak point on the posterior implant within the mandibular all-on-four assembly. The peak stress values of implant screw and implant fixture in the EHC groups were lower than the IHC group.

Rapid and visual detection of Toxoplasma gondii oocyst in cat feces using loop-mediated isothermal amplification (LAMP) assay.

Toxoplasma gondii is an obligate parasitic protozoon that transmits to animals and humans via ingested food. Cats that act as T. gondii's final hosts play a critical role in T. gondii transmission by shedding millions of oocysts. Timely diagnosis of infected cats is essential for preventing toxoplasmosis because oocysts are a putative T. gondii source in epidemiology. We developed a new visual LAMP assay targeting the B1 gene to analyze single oocysts in cat feces in this study. The amplification result could be visually estimated based on the color change. LAMP assay analytical sensitivity was 101 copies/µL for the B1 gene plasmid, which was tenfold better than the PCR reaction. There were no cross-reactions with other parasites. The LAMP assay can detect a single T. gondii oocyst in 200 mg of cat feces. The LAMP assay detected a single oocyst in 200 mg cat feces at a higher rate than the PCR assay (83.3% vs. 50.0%).

Enhancing Temperature Adaptability of Aqueous Zinc Batteries via Antifreezing Electrolyte and Site-Selective ZnSe-Ag Interface Layer Design.

Rechargeable aqueous zinc batteries (RAZBs) represent a sustainable, environmentally benign, cost-efficient energy storage solution for the scaled renewable power system. However, the cycling endurance and temperature adaptability of RAZBs are hindered by practical technological barriers such as the subzero freezing point of aqueous electrolyte, severe cation dissolution of the cathode, and dendrite growth on the Zn anode. Herein, we optimize the hybrid electrolyte formulation of 8 M ZnCl2 in the ethylene glycol-water mixed solvent to reconfigure the hydrogen bonding and [Zn(H2O)1.80(EG)0.23]2+ solvation sheath, which well balances the ionic conductivity and the antifreezing property until -125 °C. As monitored by operando X-ray diffraction, meanwhile, the structural dissolution of the V2O5 cathode upon the dynamic cycling and static idling storage at elevated temperature are effectively restrained. At the anode side, the thermally induced substitution between the Ag2Se overcoating and Zn foil in situ constructs the site-selective, mosaic interface layer, in which the solvophilic ZnSe facilitates the desolvation, while the Ag species provide zincophilic nucleation sites for high-throughput Zn deposition. The synergistic coupling of the antifreezing electrolyte and anode interfacial design enables the wide-temperature-range adaptability of the RAZB prototype (10 µm Zn foil and 1 mAh cm-2 V2O5 cathode), which balances the cycling endurance (92.5% capacity retention rate for 1000 cycles), 84.7% mitigation of the self-discharge rate at 55 °C, as well as the secured cyclability even at -40 °C.

Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis.

Introduction: Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC. Method: We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software. Results: Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58-1.19, p=0.300 and OR, 1.54; 95%CI 0.89-2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15-0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03-0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02-0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39-4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81-4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33-4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08-2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55-81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06-4.61, p=0.030). Conclusions: Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming.

Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy.

Novel mutations in PLCZ1 lead to early embryonic arrest as a male factor.

Early embryonic arrest is one of the causes of assist reproduction technology (ART) failure. We have previously reported that the first sperm-derived genetic factor, ACTL7a mutations, could lead to early embryonic arrest. However, whether there are other male genetic factors associated with early embryonic arrest remains elusive. Here, we reported bi-allelic mutations in PLCZ1, a well-known causal gene of total fertilization failure, in four infertile males. Among these mutations, p.403_404del, p.I489S, and p.W536X were newly reported in this study. Histological and Western blotting analysis of the patients' sperm indicated these variants as loss-of-function mutations. These patients manifested normal conventional semen parameters and ultra-structures in sperm heads. However, among four in vitro fertilization (IVF) cycles, 81.8% (18/22) of the oocytes were polyspermic fertilized, which was rarely reported in PLCZ1-related male patients. In the following six ICSI cycles, artificial oocyte activation (AOA) was applied and successfully rescued the fertilization failure and polyspermy phenotypes, with 31.3% (15/48) of the MII oocytes normally fertilized. However, 60.0% (9/15) of these normally fertilized zygotes were arrested at 2-5-cell stage, with one failing to cleave, indicating that PLCZ1 was not only necessary for fertilization, but also crucial for early embryonic development. However, these rescued zygotes showed a lower potential in developing into blastocysts when cultured in vitro. Thus, fresh cleavage transfer was tried and two live births were successfully achieved thereafter. In conclusion, this study provided novel mutations in PLCZ1 gene to expand the pathogenic mutational spectrum in male infertility and demonstrated that PLCZ1 was a crucial sperm-related genetic factor for early embryonic arrest. We also proposed that cleavage transfer after ICSI and AOA treatment could be a potential treatment method for male patients carrying bi-allelic mutations in PLCZ1.

Spatio-temporal pattern, matching level and prediction of ageing and medical resources in China.

OBJECTIVE: Population ageing, as a hot issue in global development, increases the burden of medical resources in society. This study aims to assess the current spatiotemporal evolution and interaction between population ageing and medical resources in mainland China; evaluate the matching level of medical resources to population ageing; and forecast future trends of ageing, medical resources, and the indicator of ageing-resources (IAR). METHODS: Data on ageing (EPR) and medical resources (NHI, NBHI, and NHTP) were obtained from China Health Statistics Yearbook and China Statistical Yearbook (2011-2020). We employed spatial autocorrelation to examine the spatial-temporal distribution trends and analyzed the spatio-temporal interaction using a Bayesian spatio-temporal effect model. The IAR, an improved evaluation indicator, was used to measure the matching level of medical resources to population ageing with kernel density analysis for visualization. Finally, an ETS-DNN model was used to forecast the trends in population ageing, medical resources, and their matching level over the next decade. RESULTS: The study found that China's ageing population and medical resources are growing annually, yet distribution is uneven across districts. There is a spatio-temporal interaction effect between ageing and medical resources, with higher levels of both in Eastern China and lower levels in Western China. The IAR is relatively high in Northwest, North China, and the Yangtze River Delta, but showed a declining trend in North China and the Yangtze River Delta. The hybrid model (ETS-DNN) gained an R2 of 0.9719, and the predicted median IAR for 2030 (0.99) across 31 regions was higher than the median IAR for 2020 (0.93). CONCLUSION: This study analyzes the relationship between population ageing and medical resources, revealing a spatio-temporal interaction between them. The IAR evaluation indicator highlights the need to address ageing population challenges and cultivate a competent health workforce. The ETS-DNN forecasts indicate higher concentrations of both medical resources and ageing populations in eastern China, emphasizing the need for region-specific ageing security systems and health service industries. The findings provide valuable policy insights for addressing a hyper-aged society in the future.

DUSP4 promotes esophageal squamous cell carcinoma progression by dephosphorylating HSP90ß.

The molecular and pathogenic mechanisms of esophageal squamous cell carcinoma (ESCC) development are still unclear, which hinders the development of effective treatments. In this study, we report that DUSP4 is highly expressed in human ESCC and is negatively correlated with patient prognosis. Knockdown of DUSP4 suppresses cell proliferation and patient-derived xenograft (PDX)-derived organoid (PDXO) growth and inhibits cell-derived xenograft (CDX) development. Mechanistically, DUSP4 directly binds to heat shock protein isoform ß (HSP90ß) and promotes the ATPase activity of HSP90ß by dephosphorylating HSP90ß on T214 and Y216. These dephosphorylation sites are critical for the stability of JAK1/2-STAT3 signaling and p-STAT3 (Y705) nucleus translocation. In vivo, Dusp4 knockout in mice significantly inhibits 4-nitrochinoline-oxide-induced esophageal tumorigenesis. Moreover, DUSP4 lentivirus or treatment with HSP90ß inhibitor (NVP-BEP800) significantly impedes PDX tumor growth and inactivates the JAK1/2-STAT3 signaling pathway. These data provide insight into the role of the DUSP4-HSP90ß-JAK1/2-STAT3 axis in ESCC progression and describe a strategy for ESCC treatment.