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Abstract Background Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long‐term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. Methods In total, 3168 participants with a 30‐year follow‐up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA‐IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15‐year event accrual period. Results The mean age of all 3168 participants was 41.0 (37.0–43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05–2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single‐factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA‐IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17–3.83, P = 0.013) (P for interaction >0.05). Conclusions Long‐term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

Abstract The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. The macrophages are considered as the most abundant immune cells in tumor microenvironment and their function in tumorigenesis is interesting. Macrophages can be present as M1 and M2 polarization that show anti-cancer and oncogenic activities, respectively. Tumor-associated macrophages (TAMs) mainly have M2 polarization and they increase tumorigenesis due to secretion of factors, cytokines and affecting molecular pathways. Hepatocellular carcinoma (HCC) is among predominant tumors of liver that in spite of understanding its pathogenesis, the role of tumor microenvironment in its progression still requires more attention. The presence of TAMs in HCC causes an increase in growth and invasion of HCC cells and one of the reasons is induction of glycolysis that such metabolic reprogramming makes HCC distinct from normal cells and promotes its malignancy. Since M2 polarization of TAMs stimulates tumorigenesis in HCC, molecular networks regulating M2 to M1 conversion have been highlighted and moreover, drugs and compounds with the ability of targeting TAMs and suppressing their M2 phenotypes or at least their tumorigenesis activity have been utilized. TAMs increase aggressive behavior and biological functions of HCC cells that can result in development of therapy resistance. Macrophages can provide cell–cell communication in HCC by secreting exosomes having various types of biomolecules that transfer among cells and change their activity. Finally, non-coding RNA transcripts can mainly affect polarization of TAMs in HCC.

Abstract Background Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. Results Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. Conclusions The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Abstract Background Developmental dysplasia of the hip (DDH) is a common childhood health complaint, whose etiology is multifactorial. The incidence of DDH is variable and higher in Tibet plateau. Here, we collected plasma samples and studied the metabolomics signatures of DDH. Methods Fifty babies were enrolled: 25 with DDH and 25 age-matched non-DDH healthy controls (HC group). We collected plasma samples, laboratory parameters and conducted untargeted metabolomics profiling. Results There are many differential metabolites among patients with DDH, including 4-β-hydroxymethyl-4-α-methyl-5-α-cholest-7-en-3-beta-ol, β-cryptoxanthin, α-tocopherol, taurocholic acid, glycocholic acid, 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, arabinosylhypoxanthine, leucyl-hydroxyproline, hypoxanthine. The main differential metabolic pathways focused on primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism, histidine metabolism, purine metabolism. Conclusions To our knowledge, this is the first report of metabolomics profile in babies with DHH. By combining the α-tocopherol and taurocholic acid, we could achieve the differential diagnosis of DDH.

Abstract Background Transforming growth factor-β (TGF-β) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-β pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-β signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. Methods This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. Results Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25–8.60 h from 5 – 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. Conclusions GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. Trial registration ClinicalTrial. gov ( https://www.clinicaltrials.gov/ ), NCT05051241. Registered on 2021-09-02.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 μg/kg for 2 cycles; then 75 μg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

Extensive research has made significant progress in exploring the potential application of extracellular vesicles (EV) in the diagnosis and treatment of osteoarthritis (OA). However, there is current a lack of study on bibliometrics. In this study, we completed a novel bibliometric analysis of EV research in OA over the past two decades. Specifically, we identified a total of 354 relevant publications obtained between January 1, 2003 and December 31, 2022. We also provided a description of the distribution information regarding the countries or regions of publication, institutions involved, journals, authors, citations, and keywords. The primary research focuses encompassed the role of extracellular vesicles in the diagnosis of OA, delivery of active ingredients, treatment strategies, and cartilage repair. These findings highlight the latest research frontiers and emerging areas, providing valuable insights for further investigations on the application of extracellular vesicles in the context of osteoarthritis.

At present, the research on spent fuel reprocessing technology, especially the research on solvent extraction technology has been paid more and more attention. The radionuclides in aqueous solution were extracted with organic diluent containing extractant. This paper aims to review and discuss the extraction performance and radiation stability of phosphorus-containing extractants, especially neutral phosphorus extractants, used in spent fuel reprocessing(solvent extraction) in the past decade. For neutral phosphine extractants, the extraction performance and radiation stability are affected by other factors such as its own structure, diluent type, etc. The decrease of the number of P—O bonds in the extractant would improve the extraction performance. The increase of alkyl chain length or the introduction of branched chain(such as methyl, ethyl and phenyl) can improve the radiation stability. In addition, the organic phase with ionic liquid as diluent can reduce the irradiation of the organic phase. Therefore, the study of the relationship between the structure of phosphorus-containing extractants and their extraction performance and radiation stability are conducive to select the extractant suitable for spent fuel reprocessing. It is also of great significance to select the structure with excellent extraction performance and radiation stability to guide the synthesis of new phosphorus-containing extractants.

Abstract. Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

Background: Serum concentration of soluble growth stimulation expressed gene 2 (sST2) appears to have prognostic value in patients with aneurysmal subarachnoid hemorrhage (aSAH) by now. This study aimed to investigate the relationship between cerebrospinal fluid (CSF) sST2 concentration and outcome in patients with aSAH. Methods: A total of 65 aSAH patients who met the inclusion criteria in the Neurosurgery Department of Jining No.1 People's Hospital from March 2021 to August 2022 were selected as the research objects. 35 patients with the third month Modified-Rankin-Scale (mRS) score of 0–2 were divided into good prognosis group, and 30 patients with the third month mRS score of 3–5 were divided into poor prognosis group. CSF was collected by lumbar puncture for the first 5 days after aneurysm surgery. CSF sST2 concentration was determined using an enzyme-linked immunosorbent assay. Results: In all patients, CSF sST2 concentrations initially increased, peaked on day 2, and then decreased. Compared with the good prognosis group, the sST2 concentration was significantly increased in the poor prognosis group at 1, 2, 3, 4 and 5 days after aSAH surgery. CSF sST2 concentration exhibited good diagnostic performance for predicting outcome (area under the receiver operating characteristic curve = 0.988). Additionally, CSF sST2 concentration has good performance for predicting cerebral edema, but only in the poor prognosis group (area under the curve = 0.93). Conclusions: Elevated CSF sST2 concentration is associated with poor outcome in aSAH patients. CSF sST2 may have a role as a predictive biomarker in these patients.

Shrub encroachment in grassland has become an ecological issue of mounting concern. Accordingly, an accurate estimation of aboveground biomass (AGB) of shrub vegetation is the basis for a sound assessment and in-depth understanding of carbon cycling in shrub-encroached grassland ecosystems. Yet the relatively low stature of plants in the shrub community, coupled with the high spatial heterogeneity of their distribution, contributes substantially to greater uncertainty in remote sensing estimation of shrub vegetation’s AGB. This study proposes a space–air-ground integrated approach to accurately estimate the AGB of shrub vegetation in shrub-encroached grassland ecosystems. The results showed that, at the UAV scale, the estimation of AGB for a monoculture shrub was highly dependent on planar geometric features. Based on the orthorectified images obtained from unmanned aerial vehicles (UAVs), four planar geometric features of shrub plants, namely crown area (S), crown perimeter (C), long-to-short crown dimension ratio (A1, A2), were retained as the most crucial predictors for AGB estimation. Among the 102 features related to vertical structure extracted via Light Detection and Ranging (LiDAR), only the crown height variation and the first layer’s density variable were retained. Utilizing the mentioned features and a random forest regression, the AGB prediction model for the shrub Caragana microphylla performed remarkably well, in having an R2 value of 0.84 and an RMSE of 310.14 g/plant. At the satellite scale, there was significant nonlinear relationship between the AGB of the shrubs and the band, texture, and index features extracted from GF-6 imagery. The derived AGB estimation model based on the Random Forest method demonstrates higher accuracy (R2 = 0.81, RMSE = 14.61 g/m2, MAE = 11.26 g/m2) than the linear stepwise regression (SR) and partial least squares regression (PLSR) models. Notably, the green band reflectance was retained in all three modeling approaches despite pronounced differences in their selected features uses. Yet both NDVIre1 and NDREI indices with red-edge bands were more important, suggesting the red-edge bands of GF-6 can serve as an ideal tool for remote sensing investigations of the AGB of shrub in shrub-encroached grasslands. This study provides technical and scientific support for quantitative assessments of shrub AGB in arid and semi-arid grassland regions.

Not available.

BackgroundEncephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication.Case presentationHerein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered.ConclusionWe should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.

Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio [HR] = 5.22, confidence interval [CI] = 1.50–18.21, P = .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.

Aiming at the problems of low processing efficiency, low groove shape accuracy and poor surface quality caused by grinding wheel wear in the grinding process of Cf/SiC composite grooves. In this paper, based on the motion mode of grinding wheel grinding, the wear volume formula of grinding wheels was analyzed, and the grinding wheel wear comparison experiment of different bond diamond grinding wheels grinding Cf/SiC composite grooves was carried out, and the more suitable kind of diamond grinding wheel for grinding Cf/SiC composite grooves was selected. From the experimental results, compared with the ceramic-bonded diamond wheel and resin-bonded diamond wheel, the grinding times of electroplated diamond wheel grinding Cf/SiC composites were increased by 20 and 104, respectively, and the surface roughness of the groove was most stable and the processing damage was smallest. Therefore, the best quality of grinding Cf/SiC composites groove was obtained by the electroplated diamond grinding wheel, and its life in grinding Cf/SiC composites was the longest. At the same time, the wear mechanism of the electroplated grinding wheel was explored, the wear on the bottom surface of the electroplated grinding wheel was more serious than that on the circumferential surface. The wear on the bottom surface was mainly wear and tear, and it gradually diffused along the inner diameter of the grinding wheel with the increasing grinding times.

This paper briefly summarized the structural characteristics of earthquake zones, the frequency of seismic activities, the number of primary and secondary school students and the volume of earthquake prevention and disaster reduction science popularization team in China. Taking “National Security Education Day for Primary and Secondary School Students” as an example, through two aspects of traditional science popularization education and new media science popularization education, seven specific forms of science popularization education are introduced, including earthquake emergency evacuation drills, lectures on science popularization knowledge, thematic research, knowledge competitions, live broadcast on mobile Internet, online education cloud platform, and intelligent digital interactive experience. These provided some valuable references for relevant functional departments of earthquake, education, emergency management, and primary and secondary schools to carry out a series of activities of earthquake prevention and disaster reduction science popularization education for primary and secondary school students. By promoting the continuous enrichment of earthquake prevention and disaster reduction science popularization forms and the continuous improvement of primary and secondary school students’ awareness and ability of earthquake prevention and disaster reduction, the broad masses of primary and secondary school students will gradually become “the future of the country” who understand earthquakes, respect earthquakes, and understand how to prevent earthquake hazards.

Dermatomyositis represents an autoimmune disorder characterized by notable skin and muscular manifestations. The annual incidence of dermatomyositis stands at approximately (5~10)/1 million individuals. Notably, patients with malignant tumors exhibit an elevated risk of developing dermatomyositis compared to the general population. However, in cases where dermatomyositis co-occurs with malignancy, the efficacy of hormone therapy alone tends to be suboptimal. Moreover, reports addressing the correlation between tumor treatment and the management of dermatomyositis are scarce. A 60-year-old male patient presented with dermatomyositis, initially manifesting through symptoms such as rash, muscle weakness, and dysphagia. Despite undergoing standard hormone therapy, there was no discernible improvement in the dermatomyositis symptoms. Considering the patient’s concomitant troublesome cough, further investigations were conducted, including CT, PET-CT, and pathological biopsy. These assessments confirmed the diagnosis of limited-stage small cell lung cancer (T1cN3M0 IIIB). Notably, in this patient, dermatomyositis was suspected to be a paraneoplastic syndrome associated with small cell lung cancer. Standard chemotherapy and radiotherapy were employed to treat the small cell lung cancer, resulting in partial remission after two treatment cycles. As the malignancy regressed, a notable improvement in dermatomyositis symptoms was observed, subsequently leading to a gradual reduction in the prescribed hormone dosage. In conclusion, we present a comprehensive case study of dermatomyositis as a paraneoplastic syndrome throughout the treatment process. The response to tumor therapy coincided with the amelioration of dermatomyositis symptoms. Therefore, diligent malignancy screening is imperative for patients diagnosed with dermatomyositis.

Background: Immune checkpoint inhibitor therapy has demonstrated impressive clinical benefits in multiple tumor types. TQB2450, a novel monoclonal antibody targeting programmed cell death ligand 1, has shown safety and efficacy in preclinical studies. Objectives: This first-in-human study aimed to evaluate the safety/tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of TQB2450 in patients with advanced malignant tumors. Design and methods: In this phase I study, eligible patients with advanced malignant tumors received intravenous TQB2450 once every 3 weeks. This study consisted of a 3 + 3 dose-escalation phase (1–30 mg/kg) and a specific dose-expansion phase (1200 mg). The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety. The secondary endpoints were PK, immunogenicity, and investigator-assessed response rate. Results: Between April 2018 and February 2020, 40 patients were enrolled (22 in the dose-escalation phase and 18 in the dose-expansion phase). No DLT was reported and the MTD was not reached. Grade ⩾3 or worse treatment-related treatment-emergent adverse events (AEs) occurred in 11 (27.50%) patients, with the most frequent being aspartate aminotransferase increased (5.00%), leukopenia (5.00%), and anemia (5.00%). Treatment-related serious AEs were reported in six patients, the most common of which was decompensated liver function (5.00%). No treatment-related death was reported. The maximum serum concentration of TQB2450 increased in a dose-proportional manner. Treatment-induced anti-drug antibodies were detected in 31.58% (12/38) of patients. The investigator assessed the objective response rate as 5.00% and the disease control rate was 52.50%, including 2 partial responses and 19 stable diseases. The median progression-free survival was 2.69 (95% confidence interval, 2.07–6.14) months. Conclusion: TQB2450 has a manageable safety profile with favorable PK and immunogenicity and has shown early evidence of clinical activity in advanced malignant tumors. ClinicalTrials.gov identifier: NCT03460457.

Ethylenediaminetetraacetic acid disodium (EDTA) can form stable complexes with many metals. To improve the leaching rate of gold and the consumption rate of thiosulfate, EDTA and ammonia were combined with copper ions to form a copper-EDTA-ammonia-thiosulfate system. Electrochemical methods were used to study the effect of thiosulfate, copper ion, EDTA, and polarization voltage. The results showed that increasing the concentrations of thiosulfate, copper ions, and EDTA promoted the dissolution of gold, which changed from electrochemical control to diffusion control after adding EDTA. The order of influence was thiosulfate > EDTA > copper ion. The pure gold leaching experiment showed that the dissolution rate of gold in the EDTA-ammonium-copper thiosulfate system was higher than that in the EDTA-copper-thiosulfuric acid system, thus achieving synergistic gold leaching.

Abstract Bacterial infections can significantly impede wound healing and pose a serious threat to the patient’s life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.

Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

Abstract Background Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI. Methods Between 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated. Results CRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P

Thiosulfate gold leaching is a green gold extraction technology. Here, the effects of thiosulfate, copper ion, ethylenediamine, and polarization voltage on the dissolution of gold in this system were investigated by an electrochemical method. The results showed that the addition of thiosulfate promoted the dissolution of gold, but increasing the thiosulfate concentration had a little additional effect. The addition of ethylenediamine also increased the dissolution of gold, but the dissolution resistance of gold increased after adding ethylenediamine. The dissolution of gold increased, the diffusion resistance increased, and the dispersion effect increased upon increasing the copper ion concentration. The copper–ethylenediamine–thiosulfate system did not display passivation (or only weak passivation) upon increasing the polarization voltage, which indicates that the system was relatively stable. The influence of three factors on the dissolution of gold followed the order thiosulfate > copper ion > ethylenediamine.

The treatment and disposal of high level liquid waste(HLLW) is an important factor affecting the sustainable development of nuclear energy. The extraction separation of high-heat-release nuclide 137Cs from HLLW is not only beneficial to the safe disposal of HLLW, but also meeting the needs of 137Cs in many industry fields. In this work, the extraction process for 137Cs from HLLW was proposed with calixcrown as extractant. The process was tested with simulated and real HLLW with a recovery percentage of 99.9% for Cs(Ⅰ) and 99.95% for 137Cs, respectively. The results show that the proposed process for Sr extraction has a bright future in the treatment of commercial HLLW and the recovery of 137Cs in China.

The electrolytic separation of actinides(An) from fission products(FPs) on solid Al cathode is one of the most promising pyrochemical reprocessing processes. In this work, the electrochemical behaviour of Pu3+ on active Al solid cathode was studied through the transient electrochemical method. Based on the results of cyclic voltammetry(CV) and square wave voltammetry(SWV), Pu3+ can be reduced into alloy through a onestep threeelectrons transfer process on Al cathode, and the reaction is irreversible. The relationship between the reduction potential of the alloy formed by Pu3+ with Al and temperature is EΘ,*(Pu3+/PuAln)(vs. Cl-/Cl2)=-2.944+9.84×10-4T. Five Pu alloys(involving Pu3Al, PuAl, PuAl2, PuAl3, and PuAl4) are formed according to the results of open circuit chronopotentiometry(OCP) together with phase diagrams of Pu-Al. Furthermore, the formation Gibbs free energies of PuAl4 at different temperature are calculated.

Fast reactor spent fuel with high burnup has the characteristics of high plutonium content, high radioactivity and high heat release rate. The aqueous reprocessing based on solvent extraction principle has the problem of solvent radiolysis. It is better to adopt the dry reprocessing. Dry reprocessing based molten salt electrolysis using irradiation-resistant inorganic salts as media, through electrochemical separation and recovery of actinide, is the most promising dry reprocessing technology. In the process of molten salt electrolytic dry reprocessing, the electrorefining unit is the core link which is responsible for the actinide separation. In this paper, the research and development progress of electrorefiner in the dry reprocessing of spent fuel is investigated, and the key technologies and development trend of electrorefiner are analyzed, which provides a reference for the research and development of fast reactor spent fuel reprocessing in China.

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.

BackgroundThis study aimed to identify potential biomarkers in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) and further probe the prognostic implications of CDKN2A mutations, particularly within a subset receiving immunotherapy.MethodsIn this retrospective single-center study, we evaluated the next-generation sequencing (NGS) data from Foundation Medicine (FM) for patients with recurrent or metastatic HNSCC between January 1, 2019, and December 31, 2021. Patients were stratified based on CDKN2A loss-of-function (LOF) versus wild-type (WT) categorizations, with a focused subgroup analysis on those administered immunotherapy.ResultsThe study encompassed 77 patients, of which 62 had undergone immunotherapy. The median duration of follow-up was 22.6 months. For the CDKN2A LOF group, the median overall survival (OS) was 16.5 months, contrasted with 30.0 months in the CDKN2A WT group (P=0.014). Notably, female gender (hazard ratio [HR]=4.526, 95% confidence interval [CI]: 1.934-10.180, P=0.0003) and CDKN2A LOF (HR=2.311, 95% CI: 1.156-4.748, P=0.019) emerged as independent risk factors for mortality in patients with recurrent or metastatic HNSCC. Within the immunotherapy subset, the median OS was 11.7 months for the CDKN2A LOF group, and 22.5 months for the CDKN2A WT group (P=0.017). Further, the female gender (HR=4.022, 95% CI: 1.417-10.710, P=0.006), CDKN2A LOF (HR=4.389, 95% CI: 1.782-11.460, P=0.002), and a combined positive score below 1 (HR=17.20, 95% CI: 4.134-79.550, P

Abstract Introduction Currently, only a few options are available for the treatment of patients with small‐cell lung cancer (SCLC) after the failure of first‐line platinum‐based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second‐line treatment of advanced SCLC. Patients and Methods This prospective clinical trial recruited patients treated with apatinib plus second‐line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression‐free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second‐line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3–4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance. Conclusion Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second‐line therapy in SCLC.

When urban distribution systems are gradually modernized, the overhead lines are replaced by underground cables, whose shunt admittances can not be ignored. Traditional power flow (PF) model with π equivalent circuit shows non-convexity and long computing time, and most recently proposed linear PF models assume zero shunt elements. All of them are not suitable for fast calculation and optimization problems of modern distribution systems with non-negligible line shunts. Therefore, this paper proposes a linearized branch flow model considering line shunt (LBFS). The strength of LBFS lies in maintaining the linear structure and the convex nature after appropriately modeling the π equivalent circuit for network equipment like transformers. Simulation results show that the calculation accuracy in nodal voltage and branch current magnitudes is improved by considering shunt admittances. We show the application scope of LBFS by controlling the network voltages through a two-stage stochastic Volt/VAr control (VVC) problem with the uncertain active power output from renewable energy sources (RESs). Since LBFS results in a linear VVC program, the global solution is guaranteed. Case study exhibits that VVC framework can optimally dispatch the discrete control devices, viz. substation transformers and shunt capacitors, and also optimize the decision rules for real-time reactive power control of RES. Moreover, the computing efficiency is significantly improved compared with that of traditional VVC methods.

Background: Patient-reported outcomes (PROs) are increasingly becoming an important part of clinical trials as they are helpful in analyzing the safety and efficacy of treatment in chronic diseases like cancer. Objectives: We report PROs and health-related quality of life (HRQoL) with selpercatinib treatment among Chinese patients with rearranged in transfection ( RET ) fusion-positive non-small-cell lung cancer (NSCLC), RET fusion-positive thyroid cancer (TC), and RET -mutant medullary TC (MTC) as an exploratory analysis of the LIBRETTO-321 trial. Design: A total of 77 patients (47 RET fusion-positive NSCLC, 1 RET fusion-positive TC, and 29 RET -mutant MTC) were enrolled. Compliance for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was 100% at baseline and >90% at each time point. Methods: PROs were assessed using the EORTC QLQ-C30, and a bowel diary assessment for MTC patients with baseline diarrhea using the Systemic Therapy-Induced Diarrhea Assessment Tool. Data were collected at pre-dose; every 8 weeks from cycle 3; and every 12 weeks after cycle 13. A >10-point change from baseline was considered clinically meaningful. PRO changes were summarized through cycle 13. Results: Most patients with NSCLC or MTC showed improvement or remained stable on the global health status and functional subscales. For global health status, 47.4% of NSCLC and MTC patients showed definite improvement with only 19.7% showing definite worsening. For functional subscales, less than 30% of the patients showed definite worsening. For symptom subscales, more than 64% of the patients either improved or remained stable for the symptoms. For MTC patients with bowel diary assessment ( n = 5), there was no severity or worsening from baseline in the diarrheal episodes observed during treatment with selpercatinib. Conclusion: The study demonstrated favorable PROs in Chinese patients with RET fusion-positive NSCLC, TC, and RET -mutant MTC treated with selpercatinib. HRQoL was improved or stable as assessed by EORTC QLQ-30. Trail registration: This study was registered at ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04280081 ) ClinicalTrials.gov Identifier: NCT04280081.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442–454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology .

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a rare malignant tumor that arises from a primary or recurrent benign pleomorphic adenoma (PA). Ca ex PA has an aggressive behavior and poor prognosis. To date, there are no standardized therapeutic methods. Herein, we reported a case of a 57-year-old Chinese female with Ca ex PA of the submandibular gland. After surgery, cervical lymph nodes recurred, and multiple distant metastases were detected. During the treatment, she received multiple chemotherapies and radiotherapy but suffered from multidrug resistance and repeated disease progression. Hence, PD-1 inhibitor (sintilimab), in combination with anlotinib, was administered, which resulted in better control of pulmonary metastases compared to the other treatment regimens. This provided an alternative treatment option for Ca ex PA of the submandibular gland patients with failed multiple therapies.

Abstract Background Pituitary stalk interruption syndrome (PSIS) is a rare disease caused by congenital pituitary anatomical defects. The underlying mechanisms remain unclear, and the diagnosis is difficult. Here, integrated metabolomics and lipidomics profiling were conducted to study the pathogenesis of PSIS. Methods Twenty-one patients with PSIS (BD group) and twenty-three healthy controls (HC group) were enrolled. Basal information and seminal plasma samples were collected. Untargeted metabolomics and lipidomics analyses were performed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results The metabolomics and lipidomics profiles of patients with PSIS changed. The prolactin signaling pathway and biosynthesis of amino acids were the main differentially modified metabolic pathways. The main differentially modified metabolites were triacylglycerols (TGs), phosphatidylethanolamine (PE), sphingomyelin (SM), ceramide (Cer) and phosphatidylcholines (PCs). Pregnenolones and L-saccharopine could achieve a diagnosis of PSIS. Conclusions Pregnenolones and L-saccharopine are potential biomarkers for a PSIS diagnosis.

Background Coronary artery calcification (CAC) is a crucial indicator of subclinical atherosclerotic cardiovascular disease. The relationship between long‐term insulin resistance (IR) trajectory and CAC has been explored in few studies. Therefore, this study aimed to investigate whether the long‐term IR time series of young adults are associated with the incidence of CAC in midlife. Methods and Results In a cohort study comprising 2777 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study, the homeostasis model assessment for IR was used to measure IR levels, and group‐based trajectory modeling was used to fit three 25‐year homeostasis model assessments for IR trajectories. Logistic regression was used to estimate the association between the 3 homeostasis model assessments for IR trajectories and CAC events at year 25. The results showed that among 2777 participants (mean age, 50.10±3.58 years; 56.2% women; 46.4% Black), there were 780 incident CAC events after a 25‐year follow‐up. After full adjustment, the prevalence of CAC was higher in the moderate‐ (odds ratio [OR], 1.40 [1.10–1.76]) and the high‐level homeostasis model assessments for IR trajectories (OR, 1.84 [1.21–2.78]) than in the low‐level trajectory. This association was observed in obese individuals despite the negative interaction between IR and different types of obesity (all P interactions >0.05). Conclusions Our study revealed that young adults with a higher level of IR were more likely to develop CAC in middle age. Furthermore, this association persisted in obese individuals. These findings highlight the importance of identifying subclinical cardiovascular risk factors and implementing primary prevention measures.

Background KN046 is a novel bispecific antibody targeting programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This multicenter phase I trial investigated the safety, tolerability, pharmacokinetics (PK), and efficacy of KN046 in patients with advanced solid tumors.Methods Patients who failed standard treatment were included. KN046 was administered at doses of 1, 3, and 5 mg/kg every 2 weeks (Q2W), 5 mg/kg every 3 weeks (Q3W), and 300 mg Q3W based on the modified toxicity probability interval method in the dose-escalation phase; the recommended dose was used in the expansion phase. Primary objectives were maximum tolerated dose (MTD) and recommended phase II dose (RP2D) in escalation and preliminary efficacy in expansion. Secondary objectives included PK, pharmacodynamics, safety, and tolerability of KN046. We also explored biomarkers based on PD-L1 expression, multiplex immunofluorescence (mIF) staining, and RNAseq-derived nCounter platform.Results Totally, 100 eligible patients were enrolled, including 59 with nasopharyngeal carcinoma (NPC), 36 with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), and those with other advanced solid tumors. The most common treatment-related adverse events (TRAEs) were rash (33.0%), pruritus (31.0%), and fatigue (20.0%). Grade ≥3 TRAEs were observed in 14.0% of participants. No dose-limiting toxicity occurred in the dose-escalation phase, and the MTD was not reached. The RP2D was determined as 5 mg/kg Q2W according to the pharmacokinetic–pharmacodynamic model, the preliminary exposure–response analysis, and the overall safety profile. Among 88 efficacy-evaluable participants, the objective response rate (ORR) was 12.5%, and the median duration of response was 16.6 months. In the NPC subgroup, the ORR was 15.4%, and the median overall survival (OS) was 24.7 (95% CI 16.3 to not estimable) months. In the EGFR-mutant NSCLC subgroup, the ORR was 6.3%. mIF analysis results showed patients with high CD8 expression showed longer median OS (27.1 vs 9.2 months, p=0.02); better prognosis was observed in patients with high CD8 and PD-L1 expression.Conclusions KN046 was well tolerated and showed promising antitumor efficacy in advanced solid tumors, especially in patients with NPC. The combination of both CD8 and PD-L1 expression improved the prediction of KN046 response.Trial registration numbers NCT03733951 .

Background: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disease, whose pathogenesis remains unclear. Here, we conducted untargeted metabolomics and lipidomics to identify seminal plasma signatures of nCHH, and to study the effect of LH and FSH deficiency on semen. Methods: Twenty-five diagnosed patients with nCHH (HH group) and twenty-three healthy participants (HC group) were enrolled. Laboratory parameters, seminal plasma samples and patients’ medical data were collected. Untargeted metabolomics and lipidomic profiling were performed using mass spectrometry (MS). Results: The metabolomics profiling are altered among patients with nCHH and healthy controls. There are 160 kinds of differential metabolites and the main different lipid species are TAG, PC, SM and PE. Conclusions: The metabolomics profiles in patients with nCHH changed. We hope that this work provides important insights into the pathophysiology of nCHH.

The dissolution process of oxides is a key step in the pyrochemical process of spent oxide fuel by electrolyzing in molten salt. The dissolved products will provide feeds for subsequent separation and recovery of U and Pu. The solubility and dissolution rate of oxides in molten salt systems are generally low. In order to meet process requirements, it is usually necessary to introduce chlorinating reagents. With different chlorinating reagents, the dissolution mechanism is quite different. Through extensive literature investigation, the related principles and characteristics of various chlorinating reagents in the chlorination process were analyzed and compared, which provided guidance for the research on chlorination and dissolution of U and Pu oxides in China.

Abstract Background R-CHOP with or without radiotherapy is the standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). To prevent overtreatment, we assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy specifically for patients with Waldeyer’s ring DLBCL. One hundred and twenty-nine patients with limited-stage DLBCL were enrolled in this open-label, nonrandomized, single-arm, phase 2 clinical trial (NCT01804127). Methods All patients were initially treated with 4 cycles of R-CHOP and underwent interim PET/CT. Patients with negative PET/CT (Deauville scores 1–2) received 2 additional cycles of rituximab monotherapy, unless they had any risk factors (primary mediastinal large B-cell lymphoma, extranodal primary or bulky disease). Otherwise, patients received another 2 cycles of R-CHOP. Patients with partial response on interim PET/CT received another 4 cycles of R-CHOP. No radiotherapy was conducted in Waldeyer’s ring DLBCL patients with negative PET/CT. The primary endpoint was 3-year progression-free survival (PFS). Overall survival (OS) in this study was compared with those from a historical study (NCT 00854568159). Results One hundred fifteen interim PET/CT scans (89.1%) were negative after 4 cycles of R-CHOP. An elevated lactate dehydrogenase level was significantly associated with positive interim PET/CT (P

The extraction of Np(Ⅳ) from nitric acid medium by using di(1-methyl-heptyl) methyl phosphonate diluted in kerosene was investigated. The influences were studied in this research including the contact time, the concentration of DMHMP, HNO3 as well as nitrate and the temperature. Slope analyses indicate that Np(Ⅳ) is coordinated mainly in the form of neutral molecules and the extractant complex is Np(NO3)4·2DMHMP. The value of enthalpy change for the reaction is negative which means that the extraction of Np(Ⅳ) is an exothermic process.

In this study, the chlorination mechanism and influencing factors of uranium oxides(mainly U3O8) were studied by using CCl4 and HCl gas as chlorination reagents respectively. The chlorination of U3O8 powder was studied with CCl4 as chlorination reagent. The mechanism and kinetic behavior of the chlorination reaction were studied by thermogravimetric analysis. The main chlorination product is UCl4. The chlorination of different types and morphologies of uranium oxide by CCl4 was also studied. The UO2 pellets are difficult to chlorinate due to their very dense structure. UO2 powder and UO3 powder are easily chlorinated by CCl4, and the chlorination products are UCl4 and UCl6 respectively. The chlorination of U3O8 powders in LiCl-KCl molten salt system was carried out using HCl gas as the chlorination reagent. The effects of reaction temperature, chlorination time, HCl gas flow rate, feeding amount of U3O8 powder, and uranium oxide types and morphologies were studied. The results show that increasing the reaction temperature, prolonging the reaction time, and increasing the HCl gas flow rate are beneficial to the improvement of the chlorination rate. The process parameters of HCl gas chlorinated U3O8 powder are recommended as follows: the chlorination reaction temperature is 500 ℃, and the flow rate of HCl gas is 0.6 L/min.

Skin wounds accompanied by massive bleeding and bacterial infection can be life-threatening and pose a significant challenge to clinical wound management. Herein, we prepared gellan gum/sericin hydrogels containing PDA-encapsulated halloysite nanotubes (halloysite@polydopamine) to achieve fast hemostasis and photothermally antibacterial effects. The morphology and compressive properties of the composite hydrogels were characterized, and the biocompatibility was investigated by hemocompatibility and cytocompatibility tests. The hemostatic properties were further evaluated in the rat liver hemorrhage and tail amputation model. The mechanical performance (compressive strength 353.2 KPa) and the hemostatic effect (30.33 ± 3.68 s in the liver injury model and 28.33 ± 2.35 s in the caudal amputation model) of the composite hydrogel were improved due to the introduction of halloysite@polydopamine. In addition, the composite hydrogel rapidly heated under 808 nm near-infrared (NIR) light irradiation, making the hydrogel extremely effective against E. coli and S. aureus. Furthermore, the wound closure rate, granulation tissue thickness, collagen deposition, and expression of inflammation-associated cytokines (CD68) and angiogenesis-associated cytokines (CD31) were investigated in a rat full-thickness skin defect model infected with S. aureus. All results showed that this multifunctional hydrogel provided better healing effects, suggesting that the composite hydrogel has become a promising alternative for infected wound repair.