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Objective: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA)., Methods: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study., Results: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05)., Conclusion: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: A phase II trial (EC-CRT-001) demonstrated the promising efficacy of combining toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) for locally advanced oesophageal squamous cell carcinoma (ESCC). Biomarkers are key to identifying patients who may benefit from this therapeutic approach., Methods: Of the 42 patients with ESCC who received toripalimab combined with definitive CRT, 37 were included in this analysis. Baseline assessments included PET/CT metabolic parameters (SUV max , SUV mean , SUV peak , MTV, and TLG), RNA sequencing of tumour biopsies to quantify the tissue mutational burden (TMB), and multiplex immunofluorescence staining to estimate immune cell infiltration in the tumour microenvironment (TME). Frozen neoplastic samples were procured for RNA sequencing to further explore the immune-related TME., Results: Among the 37 patients, high baseline SUV max (≥12.0; OR = 6.5, 95% CI 1.4-48.2, p = 0.032) and TLG (≥121.8; OR = 6.8, 95% CI 1.6-33.5, p = 0.012) were significantly correlated with lower complete response rates. All five PET/CT parameters were notably associated with overall survival; only SUV max and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUV max and TMB (R = -0.33, p = 0.062). PD-1 + CD8 + T cell infiltration was negatively correlated with MTV (R = -0.355, p = 0.034) and TLG (R = -0.385, p = 0.021). Moreover, RNA sequencing revealed that the high TLG subgroup exhibited low immune cell infiltration, indicating an immunosuppressive landscape., Conclusions: High baseline SUV max and TLG might predict poorer treatment response and worse survival in patients with ESCC undergoing immunotherapy combined with CRT. In addition, high PET/CT metabolic parameters, particularly TLG, were correlated with an immunosuppressive TME, which warrants further exploration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses., Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m 2 of paclitaxel and 25 mg/m 2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170)., Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P <  0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P <  0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P  = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P  = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs ( P  = 0.036)., Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis., Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou., Competing Interests: All authors have no conflicts of interest to declare., (© 2024 The Author(s).)

The continuous pursuit of novel two-dimensional (2D) materials with intriguing properties has been a driving force in advancing various scientific and technological frontiers. Here, based on a wide range of first-principles calculations, we predicted the existence of a novel family of 2D transition-metal oxides, the Ti 3 O M O enes (MXene-like 2D transition oxides), and determined its distinctive electronic and topological properties. A pair of 2D antiferromagnetic (AFM) Dirac points precisely located at the Fermi level in the absence of spin-orbit coupling (SOC) is observed in the 1T-Ti 3 O monolayer. Moreover, upon halogenation on a bare monolayer, 1T-Ti 3 OCl 3 and 1T-Ti 3 OBr 3 monolayers display the quantum spin Hall (QSH) effect with nontrivial helical edge states within the gapless bulk states. Specifically, single layer 1T-Ti 3 OF 3 behaves as an indirect semiconductor with a gap of 0.81 eV, exhibiting a strong light-harvesting capability. The indirect-gap feature can be switched to a direct one by only exerting a small tensile strain of 1.5%. These findings broaden emerging phenomena in a rich family of M O enes, suggesting a novel platform for the development of next-generation nanodevices.

Background: Rhodococcus equi (R. equi) is a Gram-positive zoonotic pathogen that frequently leads to illness and death in young horses (foals). This study presents the complete genome sequence of R. equi strain BJ13, which was isolated from a thoroughbred racehorse breeding farm in Beijing, China., Results: The BJ13 genome has a length of 5.30 Mb and consists of a complete chromosome and a plasmid measuring 5.22 Mb and 0.08 Mb, respectively. We predicted 4,929 coding gene open reading frames, along with 52 tRNAs and 12 rRNAs. Through analysis of mobile genetic elements, we identified 6 gene islands and 1 prophage gene. Pathogenic system analysis predicted the presence of 418 virulence factors and 225 drug resistance genes. Secretion system analysis revealed the prediction of 297 secreted proteins and 1,106 transmembrane proteins. BJ13 exhibits genomic features, virulence-associated genes, potential drug resistance, and a virulence plasmid structure that may contribute to the evolution of its pathogenicity. Lastly, the pathogenicity of the isolated strain was assessed through animal experiments, which resulted in inflammatory reactions or damage in the lungs, liver, and spleen of mice. Moreover, by the 7th day post-infection, the mortality rate of the mice reached 50.0%, indicating complex immune regulatory mechanisms, including overexpression of IL-10 and increased production of pro-inflammatory cytokines like TNF-α. These findings validate the strong pathogenicity of the isolated strain and provide insights for studying the pathogenic mechanisms of Rhodococcus equi infection., Conclusions: The complete genome sequence of R. equi strain BJ13 provides valuable insights into its genomic characteristics, virulence potential, drug resistance, and secretion systems. The strong pathogenicity observed in animal experiments underscores the need for further investigation into the pathogenic mechanisms of R. equi infection., (© 2024. The Author(s).)

Endovascular treatment has become the standard therapy for cerebral aneurysms, while the effective treatment for middle cerebral artery (MCA) bifurcation aneurysms remains a challenge. Current flow-diverting techniques with endovascular coils cover the aneurysm orifice as well as adjacent vessel branches, which may lead to branch occlusion. Novel endovascular flow disruptors, such as the Contour device (Cerus Endovascular), are of great potential to eliminate the risk of branch occlusion. However, there is a lack of valid comparison between novel flow disruptors and conventional (intraluminal) flow-diverters. In this study, two in silico MCA bifurcation aneurysm models were treated by specific Contour devices and flow-diverters using fast-deployment algorithms. Computational fluid dynamic simulations were used to examine the performance and efficiency of deployed devices. Hemodynamic parameters, including aneurysm inflow and wall shear stress, were compared among each Contour device, conventional flow-diverter, and untreated condition. Our results show that the placement of devices can effectively reduce the risk of aneurysm rupture, while the deployment of a Contour device causes more flow reduction than using flow-diverters (e.g. Silk Vista Baby). Besides, the Contour device presents the flow diversion capability of targeting the aneurysm neck without occluding the daughter vessel. In summary, the in silico aneurysm models presented in this study can serve as a powerful pre-planning tool for testing new treatment techniques, optimising device deployment, and predicting the performance in patient-specific aneurysm cases. Contour device is proved to be an effective treatment of MCA bifurcation aneurysms with less daughter vessel occlusion., (© 2024. The Author(s).)

Cross-sectional studies indicate that menstrual problems are related to poorer mental health; however, longitudinal studies are limited. This longitudinal study aimed to determine whether baseline menstrual characteristics were risk factors for incident and persistent mental health problems. The study was conducted among Chinese adolescent girls. Menstrual characteristics including menarche, menstrual cycle and menstrual pain were assessed at baseline, whereas mental health problems including PTSD, depression, anxiety, ADHD, insomnia, psychotic-like experiences, non-suicidal self-injury, suicide ideation, suicide plan, and suicide attempt were assessed at baseline (n = 1039) and at the 1-year follow-up (n = 946) by self-administered, structured questionnaires. Multiple logistic regressions were performed to examine whether menstrual characteristics were associated with incident (e.g., PTSD at follow-up but not baseline) and persistent (e.g., PTSD at both time points) mental health problems. The results demonstrated that early menarche was related to persistence of psychotic-like experiences; irregular menstruation was associated with higher rates of incident anxiety and insomnia, and persistent depression, anxiety, ADHD, insomnia, non-suicidal self-injury, suicide ideation, and suicide plan; menstrual pain was associated with elevated rates of incident PTSD and depression, and persistent depression, insomnia, psychotic-like experiences, non-suicidal self-injury, suicidal ideation, suicide plan, and suicide attempt. In conclusion, irregular menstruation and menstrual pain specifically contributed to the development of emotional problems and insomnia, and were associated with maintenance of the most mental health problems in early adolescence. The long-term effects of menstrual problems on mental health need further study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Intentional distortions of [BX 6 ] octahedra within perovskite structures have been recognized as a potent strategy for precise band gap adjustments and optimization of their photovoltaic properties, yet information regarding charge carrier dynamics linked to octahedral distortion under ambient conditions for chalcogenide perovskites remains limited. In this study, we utilize ab initio nonadiabatic molecular dynamics to explore the dynamics of photogenerated carriers in a representative two-dimensional Ba 3 Zr 2 S 7 material in the Ruddlesden-Popper phase. The theoretical results highlight the influence of octahedral rotation on the materials' stability and carrier recombination lifetime of the system. Specifically, the octahedrally rotating P 4 2 / mnm phase exhibits a prolonged nonradiative carrier recombination lifetime attributed to the stabilized electron-phonon coupling. These findings offer valuable insights into the fundamental physical characteristics of imposed octahedral distortion and its potential for optimizing the optoelectronic performance of 2D Ruddlesden-Popper Ba-Zr-S chalcogenide materials.

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran's Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach. Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007-1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019-1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859-0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918-0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008-1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02-1.098, p = 0.002). Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhou, Xu, Gao, Lou, Chen, Zhang, Fang, Tan and Huang.)

Purpose: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC)., Methods and Materials: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects., Results: In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P < .001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P < .001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P = .003; median PFS, 14.2 vs 10.6 months; P = .002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P < .001) and esophagitis (11.2% vs 2.4%, P = .006)., Conclusions: The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis., (Copyright © 2024. Published by Elsevier Inc.)

Trichomonas gallinae is a globally distributed protozoan parasite that causes avian trichomoniasis, leading to significant morbidity and mortality in birds. The present study aims to investigate the prevalence, genetic diversity, and phylogenetic relationship of T. gallinae in various bird species in Beijing. A total of 413 oropharyngeal swab samples were collected from domestic pigeons, wild pigeons, and other bird species. The overall prevalence of T. gallinae infection was 32.0% (132/413). The infection was detected in domestic pigeons, wild pigeons, and red-necked turtledoves, but not in other wild birds. Molecular analysis identified two predominant genotypes, A and B, with genotype A found in wild pigeons and genotype B found in domestic pigeons. The present study provides valuable insights on the prevalence and genetic diversity of T. gallinae in Beijing. This can be useful for understanding its pathogen distribution and host range, and the development of strategies for the prevention and control of avian trichomoniasis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In clinical practice, the determination of unbound drug concentration is very important for dose adjustment and toxicity prediction because only the unbound fraction can achieve a pharmacological effect. A fast, sensitive and accurate analytical method of centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method was developed and applied to allow the quantification of unbound lenvatinib concentration. The application of linear regression analysis was used to examine the effects of centrifugal force, centrifugal time, and protein content on ultrafiltrate volume (V u ). The results indicated that the centrifugal force and centrifugal time have an influence on V u that is significantly positive (P < 0.05). This developed method with good linearity (r 2  = 0.9996), good accuracy (bias % ≤ 2.24 %), good precision (CV % ≤ 7.10 %), and good recovery (95.46 %-106.46 %) was suitable for routine clinical practice and studies. Particularly, the ultrafiltration membrane had no non-specific binding to lenvatinib. The unbound fractions can be separated in just 15 min. This method was applied to quantify clinical samples and to determine the plasma protein binding and unbound fraction of lenvatinib. This study provides a more effective and promising method for determination of unbound lenvatinib. It could be beneficial to measure the unbound concentration of lenvatinib in personalized medicine and therapeutic drug monitoring in routine clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The psychological stress of parents and improving family quality of life (FQoL) are continuing concerns for families of children with intellectual disability. We need to identify further ways to reduce their stress and improve their FQoL in China. Method: Examine the interrelations between psychological stress, parental involvement, and FQoL for parents with intellectual disability in mainland China. 467 parents of children with intellectual disability completed instruments measuring variables. Structural equation modelling (SEM) was employed to examine the interrelations. Results: Psychological stress, directly and indirectly, influenced parental involvement in FQoL. Physical and mental response (PMR) and risk awareness (RA) had a positive direct effect on FQoL, and optimistic hope (OH) had a negative effect on FQoL. Conclusions: Psychological stress affects FQoL of parents with children with intellectual disability in complex ways. Policies should be developed to help parents with children with disability decrease stress and develop scientific parental involvement., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hydrothermal carbonization process water (HTPW) has been utilized as a substitute for chemical fertilizers in agricultural applications. However, the input of HTPW into paddy water, particularly the significant proportion of dissolved organic matter (DOM) in HTPW (DOM-HTPW), directly engages in photochemical transformations, a phenomenon often overlooked. This study observed a consistent decrease in humification (SUVA 280 , 7.7-53.9%) and aromaticity (SUVA 254 , 6.1-40.0%) of DOM-HTPW after irradiation. The primary active photobleaching components of DOM-HTPW varied depending on the feedstock, such as protein for chicken manure DOM-HTPW and lignin for rice straw DOM-HTPW. The photochemical activity of DOM-HTPW was augmented by its lower molecular weight and higher hydrophilic composition, particularly evident in chicken manure DOM-HTPW, which exhibited higher generation rates for 1 O 2 (35.1-37.1%), 3 DOM* (32.8-43.9%), and O 2 •- (28.6-48.8%) as measured by molecular probes. DOM-HTPW effectively facilitated the phototransformation of tetracycline, with the contribution of O 2 •- being more significant than 3 DOM* and 1 O 2 . These findings shed new light on the understanding the photochemical processes of DOM-HTPW as exogenous DOM and the interconnected fate of contaminants in aquatic environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of the case control study was to compare surgical outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy with the da Vinci surgical system (dVSS) and conventional vNOTES. A case control study was performed on 25 cases in our hospital. Patients (n = 8) who underwent vNOTES hysterectomy with dVSS were selected to compare with the control group (n = 17) consisted of patients who underwent conventional vNOTES. Patients in the 2 groups underwent different operations respectively, and no case was transferred to transabdominal laparoscopy. In the conventional vNOTES group, 1 patient happened intraoperative hemorrhage of about 1000 mL, and was treated with blood transfusion, and the other one of vNOTES hysterectomy with dVSS had poor incision healing within 1 month after surgery. The other patients had no intraoperative and postoperative complications. The difference of pain scores on the first day (P = .006) and the third day (P = .045) after the 2 surgical methods differed significantly. No statistical differences were observed in operation time, median hospital stay, blood loss, decreased hemoglobin 3 days after surgery, and postoperative white blood cell count. vNOTES hysterectomy with dVSS is safe and feasible, and can achieve the same effect as the conventional vNOTES hysterectomy. And this method may alleviate the pain of patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy., (© 2024. The Author(s).)

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment., (© 2023 Wiley-VCH GmbH.)

One of the most aggressive tumors arising from the skin, mucosa, and uvea is malignant melanoma, which easily metastasizes. Bone tissue is one of the most typical locations for distant metastasis, and around 5%-20% of patients eventually acquired skeletal metastases. For decades, the incidence of bone metastases was higher, bringing greater burden on the family, society, and healthcare system owing to the progress of targeted therapy and immunotherapy, which prolonging the survival time substantially. Moreover, bone metastases result in skeletal-related events, which influence the quality of life, obviously. Appropriate intervention is therefore crucial. To obtain the optimum cost-effectiveness, existing treatment algorithm must be integrated, which is still controversial. We have aimed to throw light on current views concerning the formation, biological and clinical features, and treatment protocol of melanoma bone metastases to guide the decision-making process., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis‑related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC., Methods: The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan-Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2)., Results: We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells., Conclusions: The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC., (© 2024. The Author(s).)

Chalcogenide perovskites provide a promising avenue for nontoxic, stable thermoelectric materials. Here, the thermal transport and thermoelectric properties of BaZrS 3 as a typical orthorhombic perovskite are investigated. An extremely low lattice thermal conductivity κ L of 1.84 W/mK at 300 K is revealed for BaZrS 3 , due to the softening effect of Ba atoms on the lattice and the strong anharmonicity caused by the twisted structure. We demonstrate that coherence contributions to κ L , arising from wave-like phonon tunneling, lead to an 18% thermal transport contribution at 300 K. The increasing temperature softens the phonons, thus reducing the group velocity of materials and increasing the scattering phase space. However, it simultaneously reduces the anharmonicity, which is dominant in BaZrS 3 and ultimately improves the particle-like thermal transport. In addition, via replacement of the S atom with Se- and Ti-alloying strategy, the ZT value of BaZrS 3 is significantly increased from 0.58 to 0.91 at 500 K, making it an important candidate for thermoelectric applications.

Although the efficient separation of electron-hole (e-h) pairs is one of the most sought-after electronic characteristics of materials, due to thermally induced atomic motion and other factors, they do not remain separated during the carrier transport process, potentially leading to rapid carrier recombination. Here, we utilized real-time time-dependent density functional theory in combination with nonadiabatic molecular dynamics (NAMD) to explore the separated dynamic transport path within Ruddlesden-Popper oxysulfide perovskite Y 2 Ti 2 O 5 S 2 caused by the dielectric layer and phonon frequency difference. The underlying origin of the efficient overall water splitting in Y 2 Ti 2 O 5 S 2 is systematically explored. We report the existence of the bi-directional e-h separate-path transport, in which, the electrons transport in the Ti 2 O 5 layer and the holes diffuse in the rock-salt layer. This is in contrast to the conventional e-h separated distribution with a crowded transport channel, as observed in SrTiO 3 and hybrid perovskites. Such a unique feature finally results in a long carrier lifetime of 321 ns, larger than that in the SrTiO 3 perovskite (160 ns) with only one carrier transport channel. This work provides insights into the carrier transport in lead-free perovskites and yields a novel design strategy for next-generation functionalized optoelectronic devices.

Background: Gliomas, a prevalent form of primary brain tumors, are linked with a high mortality rate and unfavorable prognoses. Disulfidptosis, an innovative form of programmed cell death, has received scant attention concerning disulfidptosis-related lncRNAs (DRLs). The objective of this investigation was to ascertain a prognostic signature utilizing DRLs to forecast the prognosis and treatment targets of glioma patients., Methods: RNA-seq data were procured from The Cancer Genome Atlas database. Disulfidptosis-related genes were compiled from prior research. An analysis of multivariate Cox regression and the least absolute selection operator was used to construct a risk model using six DRLs. The risk signature's performance was evaluated via Kaplan-Meier survival curves and receiver operating characteristic curves. Additionally, functional analysis was carried out using GO, KEGG, and single-sample GSEA to investigate the biological functions and immune infiltration. The research also evaluated tumor mutational burden, therapeutic drug sensitivity, and consensus cluster analysis. Reverse transcription quantitative PCR was conducted to validate the expression level of DRLs., Results: A prognostic signature comprising six DRLs was developed to predict the prognosis of glioma patients. High-risk patients had significantly shorter overall survival than low-risk patients. The robustness of the risk model was validated by receiver operating characteristic curves and subgroup survival analysis. Risk model was used independently as a prognostic indicator for the glioma patients. Notably, the low-risk patients displayed a substantial decrease in the immune checkpoints, the proportion of immune cells, ESTIMATE and immune score. IC50 values from the different risk groups allowed us to discern three drugs for the treatment of glioma patients. Lastly, the potential clinical significance of six DRLs was determined., Conclusions: A novel six DRLs signature was developed to predict prognosis and may provide valuable insights for patients with glioma seeking novel immunotherapy and targeted therapy., (© 2023. The Author(s).)

Background: Sunitinib (SUN) malate is an oral, multitargeted, tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. SUN has a narrow therapeutic window and high variability in interpatient pharmacokinetic parameters. Clinical detection methods for SUN and N -desethyl SUN limit the application of SUN to therapeutic drug monitoring. All published methods for quantifying SUN in human plasma require strict light protection to avoid light-induced isomerism or the use of additional quantitative software. To avoid these difficult processes in clinical routines, the authors propose a novel method that merges the peaks of the E -isomer and Z -isomer of SUN or N -desethyl SUN into a single peak., Methods: The E -isomer and Z -isomer peaks of SUN or N -desethyl SUN were merged into a single peak by optimizing the mobile phases to decrease the resolution of the isomers. A suitable chromatographic column was selected to obtain a good peak shape. Thereafter, the conventional and single-peak methods (SPM) were simultaneously validated and compared according to the guidelines published by the Food and Drug Administration in 2018 and the Chinese Pharmacopoeia in 2020., Results: The verification results showed that the SPM was superior to the conventional method in the matrix effect and met the requirements for biological sample analysis. SPM was then applied to detect the total steady-state concentration of SUN and N -desethyl SUN in tumor patients who received SUN malate., Conclusions: The established SPM makes the detection of SUN and N -desethyl SUN easier and faster without light protection or extra quantitative software, making it more appropriate for routine clinical use. The clinical application results showed that 12 patients took 37.5 mg per day, with a median total trough steady-state concentration of 75.0 ng/mL., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma., Methods and Materials: We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N = 451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant chemoradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level., Results: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P = .5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R 2  = 0.605)., Conclusions: Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is a complex and heterogeneous manifestation of multiple cardiovascular diseases that usually occurs in the advanced stages of disease progression. The role of neutrophil extracellular traps (NETs) in the pathogenesis of HF remains to be explored. Methods: Bioinformatics analysis was employed to investigate general and single-cell transcriptome sequencing data downloaded from the GEO datasets. Differentially expressed genes (DEGs) associated with NETs in HF patients and healthy controls were identified using transcriptome sequencing datasets and were subsequently subjected to functional enrichment analysis. To identify potential diagnostic biomarkers, the random forest algorithm (RF) and the least absolute shrinkage and selection operator (LASSO) were applied, followed by the construction of receiver operating characteristic (ROC) curves to assess accuracy. Additionally, single-cell transcriptome sequencing data analysis identified key immune cell subpopulations in TAC (transverse aortic constriction) mice potentially involved in NETs regulation. Cell-cell communication analysis and trajectory analysis was then performed on these key cell subpopulations. Results: We identified thirteen differentially expressed genes (DEGs) associated with NET through differential analysis of transcriptome sequencing data from HF (heart failure) samples. Utilizing the Random Forest and Lasso algorithms, along with experimental validation, we successfully pinpointed four diagnostic markers (CXCR2, FCGR3B, VNN3, and FPR2) capable of predicting HF risk. Furthermore, our analysis of intercellular communication, leveraging single-cell sequencing data, highlighted macrophages and T cells as the immune cell subpopulations with the closest interactions with neutrophils. Pseudo-trajectory analysis sheds light on the differentiation states of distinct neutrophil subpopulations. Conclusion: In this study, we conducted an in-depth investigation into the functions of neutrophil subpopulations that infiltrate cardiac tissue in TAC mice. Additionally, we identified four biomarkers (CXCR2, FCGR3B, VNN3, and FPR2) associated with NETs in HF. Our findings enhance the understanding of immunology in HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Xu, Li, Shen and Zeng.)

The search for lead-free perovskite materials has triggered intensive interest. Here, we study the electronic structures and optical properties of cation-deficient Ruddlesden-Popper oxysulfide perovskites Ln 2 Ti 2 O 5 S 2 (Ln = Sc, Y, or La), with a tunable band gap of 1.45-2.1 eV and a small exciton binding energy of ∼0.1 eV, among which Y 2 Ti 2 O 5 S 2 has been synthesized experimentally. Sc 2 Ti 2 O 5 S 2 possesses the largest light absorbance in the visible region. We further rationalize the light absorption via the transition dipole moment and suggest potential applications of Sc 2 Ti 2 O 5 S 2 in solar cells and Y 2 Ti 2 O 5 S 2 and La 2 Ti 2 O 5 S 2 in water splitting. In addition, this family exhibits small effective masses within the x - y plane and large ones along the z direction. Most importantly, electron gas-like carrier behaviors are observed within the Ti-O bond region, offering a diffusion channel for electron transport. These findings greatly advance our understanding of lead-free perovskites and offer a novel material platform for future optoelectronic devices.

Purpose: The goal of this study was to create a cleaning procedure by comparing the performance of six different cleaning methods on the surfaces in pharmacy intravenous admixture service (PIVAS) work area., Method: A stainless steel plate was simulating contaminated by gemcitabine, cyclophosphamide, epirubicin, etoposide, and paclitaxel, which was then dried and cleaned by per current cleaning protocols. The residues were collected and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Based on the most appropriate cleaning protocol, three cleaning variables were optimized: (1) use of dry gauze after cleaning agent application; (2) cleaning paths (inside-out vs. outside-in); (3) cleaning times (once or twice). Best conditions were tested with real samples from a hospital PIVAS., Results: This 10 -2  M sodium dodecyl sulfate (SDS) and dry gauze cleaning protocol increases cleaning efficiency as well as saves time. Different from the traditional cleaning manner, we found that cleaning from outside to inside can not only improve the cleaning efficiency but also overcome the uneven distribution of drug residues caused by cleaning action. When simulating contamination at a high dose (4 mg/mL) level, it was found that the decontamination efficacy increased with repeating one more time., Conclusion: The 10 -2  M SDS and dry gauze cleaning protocol could obtain the best cleaning effect. The success of cytotoxic drug decontamination is determined not only by the cleaning solution, but also by the cleaning route and frequency. Compared with the traditional cleaning manner, there was a significant reduction in the contamination levels in the PIVAS work area after the cleaning protocol with 10 -2  M SDS and dry gauze., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Definitive radiotherapy plus concurrent chemotherapy has been a standard treatment for esophagus patients who are unfit to undergo surgery. However, there are a variety of concurrent chemotherapy regimens with varying efficacy. In this phase II prospective study, we compared the efficacy and toxicity of DP (docetaxel and cisplatin) and PF (cisplatin and 5-fluorouracil) regimens with concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC) and analyzed the 5-year overall survival (OS) and progression free survival (PFS). We also summarized the salvage treatments and late toxicities., Methods: We enrolled 86 patients with clinical stage II-IVA from the Sun Yat-sen University Cancer Center. The patients were divided into two groups: PF group (41) and DP group (45). Statistics were analyzed using SPSS version 19.0., Results: The 5-year OS rates were 62.9% ± 7.6% in PF group, and 52.7% ± 7.5% in DP group (P = 0.131), respectively. The 5-year PFS rates were 43.9% ± 7.8% for PF group, and 40.0% ± 7.3% for DP group (P = 0.398), respectively. Sixteen patients in the DP group and thirteen in the PF group received salvage treatment. For those patients with local residual or local recurrent disease, the median survival time after salvage treatment was 13.5 months and the 1, 2, and 3-year survival rates were 79.0%, 50.3%, and 43.1%, respectively. For all patients, thirteen (15.1%) had Grade 2 late cardiac toxicities. One patient had Grade 2 pleural effusion and required diuretic. Most patients with pneumonia are mild, and only one patient in PF group had Grade 2 pneumonia. One patient in the DP group developed tracheoesophageal fistula., Conclusions: The 5-year follow-up confirmed that definitive CCRT with the DP regimen did not improve the treatment response, OS, or PFS in patients with ESCC compared to the PF regimen. The PF regimen remains the standard regimen for definitive CCRT for patients with locally advanced ESCC. Long-term follow-up also suggested that appropriate and active salvage treatment has a survival benefit for some patients, and late cardiopulmonary toxicities should be noticed during follow-up., Trial Registration: The trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT02969473, October 2010)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Gut microbiota and their secreted metabolites have an influence on the initiation and progression of colon cancer. Probiotics are extensively perceived as a potential microbiota-modulation strategy to promote the health of the host, while the effectiveness of preventing colon cancer based on microbiota therapy has not been confirmed, and antitumor mechanisms influenced by microbiota and their metabolites with the intervention of probiotics remain to be further investigated. In vitro , Lactobacillus (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of Lactobacillus and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by Lactobacillus in colon cancer models in mice. We demonstrated that the pre-administration of Lactobacillus (JY300-8 and JMR-01) for 20 days before establishing tumor models resulted in an 86.21% reduction in tumor formation rate compared to tumor control group. Subsequently, continuous oral administration of living Lactobacillus significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that Lactobacillus suppresses colonic tumorigenesis and progression through the modulation of gut microbiota homeostasis and metabolites, including the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P), and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Additionally, metabolome analyses of Lactobacillus (JY300-8 and JMR-01) indicate that living Lactobacillus could reduce the relative abundance of alanine and L-serine to suppress tumor progression by regulating the tumor microenvironment, including down-regulation of pyrimidine metabolism and S1P signaling in cancer. These findings provide a potential prevention strategy and therapeutic target for colon cancer through the intervention of dietary Lactobacillus . IMPORTANCE The modulation of gut microbiota and metabolites has a significant influence on the progression of colon cancer. Our research indicated that the intervention of probiotics is a potentially feasible strategy for preventing colon cancer. We have also revealed the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites, which could lead to broader biomedical impacts on the prevention and therapy of colon cancer with microbiota-based therapy regulated by probiotics.

Na 3 PS 4 crystals with high ionic conductivity are promising solid-state electrolytes. Here, a novel phase of Na 3 PS 4 ( β '-NPS) crystallizing in a cubic lattice with a space group of P 4̄3 m was systematically investigated using first-principles calculations. First of all, β '-NPS is determined to be thermodynamically, dynamically and mechanically stable. The phase transition from tetragonal Na 3 PS 4 (α -NPS) to a cubic β '-NPS system occurs at approximately 480 K, suggesting high feasibility of experimental access. Moreover, the β '-NPS is an insulator with a large band gap of 4.05 eV and a low migration energy barrier of 0.10 eV for an interstitial Na ion. Significantly, a novel Na ion diffusion mechanism, that is, interstitial diffusion, is proposed, in contrast to traditional vacancy diffusion or kick-off diffusion as observed in most solid electrolytes. This work proposes β '-NPS as a promising superionic conductor for sodium ion batteries and provides theoretical guidance towards designing future ideal solid-state electrolytes.

Background: To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m 2 and cisplatin 25 mg/m 2 on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6-8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041., Findings: All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35-65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P  = 0.19)., Interpretation: Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted., Funding: National Natural Science Foundation of China., Competing Interests: All authors have no conflicts of interest to declare., (© 2023 The Author(s).)

Background: This phase I study aimed to assess the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin-bound (nab)-paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab-paclitaxel (60 mg/m 2 , 75 mg/m 2 , and 90 mg/m 2 ) and cisplatin (25 mg/m 2 ) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50-64 Gy. The primary endpoint was the safety of chemotherapy., Results: The study enrolled 12 patients across three dose levels. No treatment-related deaths occurred. One patient in the 60 mg/m 2 dose level occurred dose-limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m 2 dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m 2 based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1-2 of 66.7% and Grade 3-4 of 33.3%), neutropenia (Grade 1-2 of 91.7% and Grade 3-4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%., Conclusions: Weekly schedule of cisplatin and nab-paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab-paclitaxel for further studies is 75 mg/m 2 ., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Esophageal squamous cell carcinoma (ESCC) is the most common esophageal malignancy, and RNA methylation has been reported to be involved in the tumorigenesis of ESCC. However, no study has explored methylation modifications in m 1 A and m 7 G as prognostic markers for survival prediction in ESCC., Methods: Public gene-expression data and clinical annotation of 254 patients obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases were analyzed to identify potential consensus clusters of m 1 A and m 7 G modification-related genes. The RNA-seq of 20 patients in Sun Yat-Sen University Cancer Center was used as the validation set. Following screening for relevant differentially expressed genes (DEGs) and enrichment pathways were elucidated. DEGs were used to construct risk models using the randomForest algorithm, and the prognostic role of the models was assessed by applying Kaplan-Meier analysis. Extent of immune cell infiltration, drug resistance, and response to cancer treatment among different clusters and risk groups were also evaluated., Results: Consensus clustering analysis based on m 1 A and m 7 G modification patterns revealed three potential clusters. In total, 212 RNA methylation-related DEGs were identified. The methylation-associated signature consisting of 6 genes was then constructed to calculate methylation-related score (MRScore) and patients were dived into MRScore-high and MRScore-low groups. This signature has satisfied prognostic value for survival of ESCC (AUC = 0.66, 0.67, 0.64 for 2-, 3-, 4- year OS), and has satisfied performance in the validation SYSUCC cohort (AUC = 0.66 for 2- and 3-year OS). Significant correlation between m 1 A and m 7 G modification-related genes and immune cell infiltration, and drug resistance was also observed., Conclusions: Transcriptomic prognostic signatures based on m 1 A and m 7 G modification-related genes are closely associated with immune cell infiltration in ESCC patients and have important correlations with the therapeutic sensitivity of multiple chemotherapeutic agents., (© 2023. The Author(s).)

Background: The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC)., Patients and Methods: Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed., Results: With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED <60 Gy (80.1% vs. 63.4%, P = .004; 68.3% vs. 33.0%, P < .001). On multivariate analysis, BED was an independent prognostic factor for both FFLP and OS., Conclusions: SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation., Methods: we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation., Results: Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05)., Conclusion: In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Toripalimab is a PD-1 inhibitor that is approved for the treatment of advanced oesophageal squamous cell carcinoma, but its efficacy in locally advanced disease is unclear. We administered toripalimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the activity and safety of this regimen, and potential biomarkers., Methods: EC-CRT-001 was a single-arm, phase 2 trial done at Sun Yat-sen University Cancer Center (Guangzhou, China). Patients aged 18-70 years with untreated, unresectable, stage I-IVA oesophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (50·4 Gy in 28 fractions), chemotherapy (five cycles of weekly intravenous paclitaxel [50 mg/m 2 ] and cisplatin [25 mg/m 2 ]), and toripalimab (240 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the complete response rate at 3 months after radiotherapy by investigator assessment. Secondary endpoints were overall survival, progression-free survival, duration of response, quality of life (not reported here), and safety. All enrolled patients were included in the activity and safety analyses. The trial is registered with ClinicalTrials.gov, NCT04005170; enrolment is completed and follow-up is ongoing., Findings: Between Nov 12, 2019, and Jan 25, 2021, 42 patients were enrolled. The median age was 56 years (IQR 53-63), 39 (93%) of 42 patients had stage III or IVA disease, and 32 (76%) patients were male and 10 (24%) were female. 40 (95%) of 42 patients completed the planned chemoradiotherapy and 26 (62%; 95% CI 46-76) of 42 had a complete response. The median duration of response was 12·1 months (95% CI 5·9-18·2). After a median follow-up of 14·9 months (IQR 11·9-18·4), 1-year overall survival was 78·4% (95% CI 66·9-92·0) and 1-year progression-free survival was 54·5% (41·3-72·0). The most common grade 3 or worse adverse event was lymphopenia (36 [86%] of 42). One (2%) patient died from treatment-related pneumonitis., Interpretation: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation., Funding: National Natural Science Foundation of China and Sci-Tech Project Foundation of Guangzhou., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The molecular mechanisms of esophageal squamous cell carcinoma (ESCC) remain poorly understood. Transmembrane emp24 trafficking protein 3 (TMED3) acts as an oncogene or tumor suppressor gene in different cancers. Our study was to explore the clinicopathological significance and functional roles of TMED3 in ESCC., Methods: Immunohistochemistry, qPCR, and western blotting were used to analyze the expression of TMED3 in ESCC tissues and cells. Statistical analysis was performed to analyze the relationship between TMED3 expression and tumor characteristics in patients with ESCC. The role of TMED3 in vitro and in vivo was investigated by performing functional verification experiments and using a xenograft mouse model. Proteins that are functionally related to TMED3 were recognized by Affymetrix microarray and Ingenuity Pathway Analysis (IPA). Functional verification experiments were performed to analyze the role of FAM60A (a protein functionally related to TMED3) in vitro., Results: We confirmed the overexpression of TMED3 was correlated with poor prognosis in ESCC patients. When TMED3 was knocked down, ESCC cell proliferation, migration, and invasion were inhibited whereas cell apoptosis was promoted in vitro, and tumorigenicity was inhibited in vivo. We further revealed significant changes in gene expression profile in TMED3 knockdown cells. Among these differentially expressed genes, FAM60A was overexpressed in ESCC tissues. Furthermore, knocking down FAM60A significantly weakened the proliferation ability of ESCC cells and reversed TMED3's tumorigenicity of ESCC cells., Conclusion: Our study revealed an oncogenic role of TMED3 in ESCC., Competing Interests: Conflicts of interest All the authors declare that they have no competing interests., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Low-dimension perovskite materials have attracted wide attention due to their excellent optical properties and stability. Herein, Sb 3+ -doped Cs 2 ZrCl 6 crystals are synthesized by a coprecipitation method in which Sb 3+ ions partially replace Zr 4+ ions. The Cs 2 ZrCl 6 : x Sb 3+ powder shows blue and orange-red emissions under a 254 and 365 nm light, respectively, due to the [ZrCl 6 ] 2- octahedron and [SbCl 6 ] 3- octahedron. The photoluminescence quantum yield (PLQY) of Cs 2 ZrCl 6 : x Sb 3+ ( x = 0.1) crystals is up to 52.5%. According to experimental and computational results, the emission mechanism of the Cs 2 ZrCl 6 : x Sb 3+ crystals is proposed. On the one hand, a wide blue emission with a large Stokes shift is caused by the self-trapping excitons of [ZrCl 6 ] 2- octahedra under a 260 nm excitation. On the other hand, the luminescence mechanism of [SbCl 6 ] 3- octahedron is divided into two parts: 1 P 1 → 1 S 0 (490 nm) and 3 P 1 → 1 S 0 (625 nm). The broad-band emission, high PLQY, and excellent stability endow the Cs 2 ZrCl 6 : x Sb 3+ powders with the potential for the fabrication of white light-emitting diodes (WLEDs). A WLED device is fabricated using a commercial 310 nm NUV chip, which shows a high color rendering index of 89.7 and a correlated color temperature of 5333 K. In addition, the synthesized Cs 2 ZrCl 6 : x Sb 3+ crystals can be also successfully used for information encryption. Our work will provide a deep understanding of the photophysical properties of Sb 3+ -doped perovskites and facilitate the development of Cs 2 ZrCl 6 : x Sb 3+ crystals in encrypting multilevel optical codes and WLEDs.

Bulk III-nitride materials MN (M = Al, Ga and In) and their alloys have been widely used in high-power electronic and optoelectronic devices, but stable two-dimensional (2D) III-nitride materials, except h-BN, have not been realized yet. A new kind of 2D III-nitride material M2Si2N4 (M = Al, Ga and In) is predicted by choosing Si as the appropriate passivation element. The stability, electronic and optical properties of 2D M2Si2N4 materials are studied systematically based on first-principles calculations. The results show that Al2Si2N4 and Ga2Si2N4 are found to be indirect bandgap semiconductors, while In2Si2N4 is a direct bandgap semiconductor. Moreover, Al2Si2N4 and In2Si2N4 have good absorption ability in the visible light region, while Ga2Si2N4 is an ultraviolet-light-absorbing material. Furthermore, the carrier lifetimes of Ga2Si2N4 and In2Si2N4 are as large as 157.89 and 103.99 ns, respectively. All these desirable properties of M2Si2N4 materials make them attractive for applications in electronics and photoelectronics.

Background: Crocetin is a bioactive ingredient in saffron, derived from the Crocus sativus stigmas of the Iridaceae family. As a chemically carotenoid derivative, crocetin exhibites effects like anti-inflammatory, antioxidant, neuroprotective, etc. However, the protective effect of crocetin on glaucoma and its mechanism remains unclear. The current study assesed the neuroprotective and anti-inflammatory effects of crocetin on retinal neurons in glaucoma rats which were induced by 0.3% carbomer injection into the anterior chamber., Methods and Results: The pathological structures on the retina and optic nerve were observed and examined by H&E staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression of TNF-α, IL-1β, and IL-6 of the retina and the expression of a brain-derived neurotrophic factor (BDNF) in the primary visual cortex (PVC). Western blot was carried out to detect the expression of PI3K, Akt, and NF-κB in the retina. It was found that crocetin ameliorated the pathological changes of the retina and ON and reduced the number of apoptotic retinal ganglion cells. Immunohistochemical staining showed that crocetin could decrease the contents of TNF-α, IL-1β, and IL-6 and increase the contents of BDNF. Western blot showed that crocetin was found to suppress the expression of PI3K, Akt, and NF-κB., Conclusion: The results obtained in this study have indicated that crocetin showes neuroprotective effects on retinal ganglion cells in glaucoma rats and inhibits retinal dysfunction. Meanwhile, crocetin exerted an anti-inflammatory effect to protect the retina by inhibiting the expression of the PI3K/Akt/NF-κB signaling pathway. This work provides substantial evidence that crocetin may be a potential drug for the treatment of glaucoma., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

In October 2021, a wild bird-origin H3N8 influenza virus-A/Chinese pond heron/Jiangxi 5-1/2021 (H3N8)-was isolated from Chinese pond heron in China. Phylogenetic and molecular analyses were performed to characterize the genetic origin of the H3N8 strain. Phylogenetic analysis revealed that eight gene segments of this avian influenza virus H3N8 belong to Eurasian lineages. HA gene clustered with avian influenza viruses is circulating in poultry in southern China. The NA gene possibly originated from wild ducks in South Korea and has the highest homology (99.3%) with A/Wild duck/South Korea/KNU2020-104/2020 (H3N8), while other internal genes have a complex and wide range of origins. The HA cleavage site is PEKQTR↓GLF with one basic amino acid, Q226 and T228 at HA preferentially bind to the alpha-2,3-linked sialic acid receptor, non-deletion of the stalk region in the NA gene and no mutations at E627K and D701N of the PB2 protein, indicating that isolate A/Chinese pond heron/Jiangxi 5-1/2021 (H3N8) was a typical avian influenza with low pathogenicity. However, there are some mutations that may increase pathogenicity and transmission in mammals, such as N30D, T215A of M1 protein, and P42S of NS1 protein. In animal studies, A/Chinese pond heron/Jiangxi 5-1/2021 (H3N8) replicates inefficiently in the mouse lung and does not adapt well to the mammalian host. Overall, A/Chinese pond heron/Jiangxi 5-1/2021 (H3N8) is a novel wild bird-origin H3N8 influenza virus reassortant from influenza viruses of poultry and wild birds. This wild bird-origin avian influenza virus is associated with wild birds along the East Asian-Australasian flyway. Therefore, surveillance of avian influenza viruses in wild birds should be strengthened to assess their mutation and pandemic risk in advance.

Background: Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This study explored correlations of clinical factors and dose-volume histogram (DVH) parameters with postoperative cardiopulmonary complications and predicted their risk by establishing a nomogram model., Methods: Clinical and DVH parameters of ESCC patients who underwent trimodality treatment from 2002 to 2020 were collected. Postoperative cardiopulmonary complications were recorded. Logistic regression analysis was applied, and a nomogram model was constructed. Area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve analyses were performed to evaluate the performance of the nomogram., Results: Of the 307 ESCC patients enrolled in this study, 65 (21.2%) experienced pulmonary complications and 57 (18.6%) experienced cardiac complications. The following six risk factors were identified as independent risk factors for pulmonary complications by multivariate logistic regression analyses in the integrated model: male sex (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.27-9.70; P = 0.021), post-radiation therapy (RT) forced expiratory volume in 1 s (FEV1) (OR, 0.51; 95% CI 0.28-0.90; P = 0.023), mean lung dose (MLD) (OR, 1.13; 95% CI 1.01-1.28; P = 0.041), and pre-RT monocyte (OR, 8.36; 95% CI 1.23-11.7; P = 0.03). The AUC of this integrated model was 0.705 (95% CI 0.64-0.77). The paclitaxel and cisplatin (TP) concurrent chemotherapy regimen was the independent predictor of cardiac complication (OR, 2.50; 95% CI 1.22-5.55; P = 0.016)., Conclusions: For ESCC patients who underwent trimodality treatment, male sex, post-RT FEV1, MLD, and pre-RT monocyte were confirmed as significant predictors of postoperative pulmonary complications. A nomogram model including six risk factors was further established. The independent predictor of cardiac complication was TP concurrent chemotherapy., (© 2022. Society of Surgical Oncology.)

The trade-off between light absorption and carrier transport in semiconductor thin film photoelectrodes is a major limiting factor of their solar-to-hydrogen efficiency for photoelectrochemical water splitting. Herein, we develop a heterogeneous doping strategy that combines surface doping with bulk gradient doping to decouple light absorption and carrier transport in a thin film photoelectrode. Taking La and Mg doped Ta 3 N 5 thin film photoanode as an example, enhanced light absorption is achieved by surface La doping through alleviating anisotropic optical absorption, while efficient carrier transport in the bulk is maintained by the gradient band structure induced by gradient Mg doping. Moreover, the homojunction formed between the La-doped layer and the gradient Mg-doped layer further promotes charge separation. As a result, the heterogeneously doped photoanode yields a half-cell solar-to-hydrogen conversion efficiency of 4.07%, which establishes Ta 3 N 5 as a leading performer among visible-light-responsive photoanodes. The heterogeneous doping strategy could be extended to other semiconductor thin film light absorbers to break performance trade-offs by decoupling light absorption and carrier transport., (© 2022. The Author(s).)

Dry eye disease (DED) is the most common clinical ocular surface disease. Given its multifactorial etiology, no consensus has been reached on the diagnosis criteria for dry eye disease. Topical drug administration remains the mainstay of treatment but is limited to the rapid clearance from the eye surface. To address these problems, hydrogel-based materials were designed to detect biomarkers or act as drug delivery systems by taking advantage of their good biocompatibility, excellent physical and mechanical properties, and long-term implant stability. Biosensors prepared using biocompatible hydrogels can be sensitive in diagnosing DED, and the designed hydrogels can also improve the drug bioavailability and retention time for more effective and long-term treatment. This review summarizes recent advances in the use of hydrogels for diagnosing and treating dry eye, aiming to provide a novel reference for the eventual clinical translation of hydrogels in the context of dry eye disease.

Rationale: Depression is a serious mood disorder, and crocetin has a variety of pharmacological activities, including antidepressant effect. The alterations of intestinal flora have a significant correlation with depression, and crocetin can alter the composition of intestinal flora in mice with depression-like behaviors., Objective: This study investigated the underlying antidepressant mechanisms of crocetin through multi-omics coupled with biochemical technique validation., Methods: Chronic unpredictable stress (CUMS) was used to induce mice model of depression to evaluate the antidepressant effect of crocetin through behavioral tests, and the metagenomic and metabolomic were used to explore the potential mechanisms involved. In order to verify its underlying mechanism, western blot (WB), Elisa, immune histological and HPLC techniques were used to detect the level of inflammatory cytokines and the level of metabolites/proteins related to tryptophan metabolism in crocetin-treated mice., Results: Crocetin ameliorated depression-like behaviors and increased mobility in depressive mice induced by CUMS. Metagenomic results showed that crocetin regulated the structure of intestinal flora, as well as significantly regulated the function gene related to derangements in energy metabolism and amino acid metabolism in mice with depression-like behaviors. Metabolomic results showed that the tryptophan metabolism, arginine metabolism and arachidonic acid metabolism played an essential role in exerting antidepressant-like effect of crocetin. According to multi-omics approaches and validation results, tryptophan metabolism and inflammation were identified and validated as valuable biological processes involved in the antidepressant effects of crocetin. Crocetin regulated the tryptophan metabolism in mice with depression-like behaviors, including increased aryl hydrocarbon receptor (AhR) expression, reduced indoleamine 2,3-dioxygenase 1 (IDO1) and serotonin transporter (SERT) expression in the hippocampus, elevated the content of 5-HT, kynurenic acid in serum and 5-HT, tryptophan in hippocampus. In addition, crocetin also attenuated inflammation in mice with depression-like behaviors, which presented with reducing the production of inflammatory cytokines in serum and colon. Meanwhile, crocetin up-regulated the expression of zonula occludens 1 (ZO-1) and occludin in ileum and colon to repair the intestinal barrier for preventing inflammation transfer., Conclusion: Our findings clarify that crocetin exerted antidepressant effects through its anti-inflammation, repairment of intestinal barrier, modulatory on the intestinal flora and metabolic disorders, which further regulated tryptophan metabolism and impacted mitogen-activated protein kinase (MAPK) signaling pathway to enhance neural plasticity, thereby protect neural., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine risk factors, treatment outcomes, and prognostic factors for esophageal fistula (EF) in patients with esophageal squamous cell carcinoma (ESCC) during radiotherapy., Methods: Between 2010 and 2018, 109 patients with EF during radiotherapy were retrospectively collected. A controlled cohort including 416 patients who received definitive chemoradiotherapy without EF was used to compare risk factors and survival outcomes. Univariate and multivariate logistic regression analyses were performed to identify predictors of EF. Propensity score matching (PSM) was applied to adjust for potential confounding factors., Results: Multivariate analysis demonstrated that sex, body mass index, alcohol history, esophageal ulceration, primary tumor length, T stage, and absolute lymphocyte count were independent risk factors for EF. After PSM, patients with EF showed remarkably worse prognosis than those without EF (median overall survival: 13.0 versus 20.5 months; P = 0.009). For patients with EF, serum albumin level (≥ 35 g/L), subsequent radiotherapy, and fistula closure were associated with significantly prolonged survival. In addition, esophageal-mediastinum fistula and subsequent radiotherapy were positive predictors for fistula closure., Conclusions: We identified risk factors for radiotherapy-related EF and its unfavorable prognosis in patients with ESCC. Of them, patients with serum albumin level of ≥ 35 g/L, subsequent radiotherapy after EF, and fistula closure had a more favorable survival., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Although Ti 3 C 2 T x MXene is a promising material for many applications such as catalysis, energy storage, electromagnetic interference shielding due to its metallic conductivity and high processability, it's poor resistance to oxidation at high temperatures makes its application under harsh environments challenging. Here, we report an air-stable Ti 3 C 2 T x based composite with extracted bentonite (EB) nanosheets. In this case, oxygen molecules are shown to be preferentially adsorbed on EB. The saturated adsorption of oxygen on EB further inhibits more oxygen molecules to be adsorbed on the surface of Ti 3 C 2 T x due to the weakened p-d orbital hybridization between adsorbed O 2 and Ti 3 C 2 T x , which is induced by the Ti 3 C 2 T x /EB interface coupling. As a result, the composite is capable of tolerating high annealing temperatures (above 400 °C for several hours) both in air or humid environment, indicating highly improved antioxidation properties in harsh condition. The above finding is shown to be independent on the termination ratio of Ti 3 C 2 T x obtained through different synthesis routes. Utilized as terahertz shielding materials, the composite retains its shielding ability after high-temperature treatment even up to 600 °C, while pristine Ti 3 C 2 T x is completely oxidized with no terahertz shielding ability. Joule heating and thermal cycling performance are also demonstrated., (© 2022. The Author(s).)

Dissolved organic matter (DOM) plays a critical role in the global carbon cycle and provides food and energy for aquatic organisms. Recently, hydrochar, as a solid carbonaceous substance derived from hydrothermal carbonization, has been increasingly used as a soil amendment. Upon entering the soil, dissolved components (DHCs) were released from hydrochar as exogenous DOM, finally entering the aquatic ecosystems by runoff, which participates in environmental geochemical processes. However, relevant reports revealing the response of the aquatic ecosystem to the input of DHCs remain insufficiently elucidated. For the first time, the fundamental features of DHCs and their influence on water quality and aquatic biological function were investigated in this study. DHCs at 260 °C (DHC260) had lower yields, a greater [C/N], worse biodegradability, and larger humic acid relative amounts than did DHCs at 180 °C (DHC180). The DHC structural alterations in periphyton-incubated aquatic ecosystems suggested that protein substances were more easily degraded or assimilated by periphyton, especially for DHC180, with rates of decrease of 34.5-63.5%. The increased chemical oxygen demand (COD) degradation in the DHC260 treatments was most likely due to humic acid substances with higher COD equivalents. Furthermore, DHC260 caused phosphorus to accumulate in periphyton, reducing aquatic phosphorus concentration. Notably, the abundances of Flavobacteria and Cyanobacteria associated with water blooms increased 12.7-25.5- and 1.3-8.3-fold, respectively; consequently, the promotional impact of DHCs on algal blooms should be considered. This result extends the nonnegligible role of DHCs in aquatic ecosystems and underlines the need to regulate the hydrochar application process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The physiological function and prognostic significance of C-type lectin domain family 12 member A (CLEC12A) in acute myeloid leukemia (AML) patients are unclear. CLEC12A transcriptional expression in a variety of tumors from several public databases was collected and compared. We found that CLEC12A was highly expressed in AML cell lines and in tissues from AML patients and a higher CLEC12A expression in leukemia stem cells. CLEC12A low expression was associated with poor prognosis in the chemotherapy-only group and high CLEC12A expression may benefit from autologous or allogeneic hematopoietic stem cell transplantation (HSCT). CLEC12A expression was positively correlated with infiltrating levels of type 2 macrophages and monocytes and negatively associated with NK cells and regulatory T cells in AML. CLEC12A high was positively associated with immune checkpoint genes as well as macrophage associated genes. CLEC12A is an ideal chimeric antigen receptor T-cell (CAR-T) therapy target for AML and its expression level was closely linked to treatment response and patients' survival outcome. CLEC12A plays an important immunomodulatory role in AML.