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Background: The log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy., Method: A total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan-Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms., Results: Multivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052-3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084-2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297-2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030)., Conclusion: The prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy., (© 2024. The Author(s).)

Background: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy., Methods: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis., Results: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients., Conclusion: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection, and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HVKP)strains., Methods: A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019, of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae (CRKP) and 96 were carbapenem-sensitive Klebsiella pneumoniae (CSKP). The drug susceptibility was detected by VITEK-2 automatic microbial analyzer; carbapenemase genes, virulence genes and capsule typing were detected by polymerase chain reaction; the high viscosity phenotype of strains was detected by string test, and the genome characteristics of CR-HVKP were detected by whole genome sequencing. Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP., Results: There were significant differences in drug resistance to common antibiotics, except for minocycline between CSKP and CRKP isolates (all P <0.05). 92 out of 96 CRKP isolates carried carbapenemase genes, mainly bla KPC - 2 . The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP ( P <0.05). The detection rates of virulence genes Kfu , aerobictin , iutA , ybtS , rmpA , magA , allS , and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group (all P <0.05). One HVKP strain was detected in the CRKP group (CR-HVKP) and 36 HVKP was detected in the CSKP group ( P <0.05). The CR-HVKP strain belonged to the MLST412, serotype K57, expressed iutA , entB , mrkD , fimH , and rmpA virulence genes, and showed strong biofilm formation and significantly increased serum resistance. Whole genome sequencing results showed that this CR-HVKP isolate carried bla SHV - 145 , bla TEM - 1 , bla CTX - M - 3 , fosA6 , oqxA5 , oqxB26 , and aac(3) - IId resistance genes, accompanied by abnormalities in outer membrane protein K (OmpK) 35 and OmpK36., Conclusions: The drug resistance of CRKP is significantly higher than that of CSKP, while CRKP carrying fewer virulence genes in both number and types compared to CSKP. A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected, which requires clinical awareness and epidemiological monitoring.

Although the safety and short-term outcomes of robotic surgery for sigmoid colon and rectal cancer patients are well-documented, there is limited research on the long-term survival outcomes of robotic colorectal surgery. This is a retrospective study that includes 502 patients who underwent either laparoscopic or robotic anterior resection and abdominoperineal resection for rectal or sigmoid colon cancer between August 2016 and September 2021. All patients were diagnosed with rectal or sigmoid colon adenocarcinoma. Propensity score matching (PSM) was implemented to minimize selection bias. Perioperative outcomes, complication rates, and pathological data were evaluated and compared. The 5-year overall survival rate and disease-free survival rate were calculated and compared. Before matching, patients in the robotic group had earlier pathological T and N stages and were more likely to have received neoadjuvant chemoradiotherapy compared to the laparoscopic group. After matching, most clinicopathological outcomes were similar between the two groups, but the robotic group had longer operative times and a lower conversion rate to open surgery compared with laparoscopic group. After matching for clinical factors, the 5-year DFS rates were 88.19% for the robotic group and 82.46% for the laparoscopic group (P = 0.122), and the OS rates were 90.5% and 79.5% (P = 0.342), showing no significant differences. In the stratified analysis, patients in the robotic surgery group had significantly higher 5-year DFS rates in the following subgroups: age < 65 years, TNM stage I-II, received neoadjuvant therapy, and primary tumor located in the rectum. The safety and efficacy of robotic surgery for sigmoid colon and rectal cancer were validated compared to laparoscopic surgery, with both groups of patients exhibiting comparable long-term prognoses., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Prostate cancer (PCa) is a leading cause of cancer-related death in men. Understanding the proteomic landscape associated with PCa risk can provide insights into its molecular mechanisms and pave the way for potential therapeutic interventions., Methods: A proteome-wide Mendelian randomization (MR) analysis was employed to determine associations between genetically predicted protein concentrations in plasma and PCa risk. From an initial list of 4,364 proteins, significant associations were identified and validated. Multiple sensitivity analyses were also conducted to enhance the robustness of our findings., Results: Of the 4,364 genetically predicted proteins, 308 exhibited preliminary associations with PCa risk. After rigorous statistical refinement, genetically predicted concentrations of 14 proteins showed positive associations with PCa risk, with odds ratios spanning from 1.55 (95% CI 1.28-1.87) for ATG4B to 2.67 (95% CI 1.94-3.67) for HCN1. In contrast, genetically predicted concentrations of ATG7, B2M, MSMB, and TMEM108 demonstrated inverse associations with PCa. The replication analysis further substantiated positive associations for MDH1 and LSM1, and a negative one for MSMB with PCa. A meta-analysis harmonizing primary and replication data mirrored these findings. Furthermore, the MVMR analysis pinpointed B2M and MSMB as having significant associations with PCa risk., Conclusion: The genetic evidence unveils a refined set of proteins associated with PCa risk. The findings underscore the potential of these proteins as molecular markers or therapeutic targets for PCa, calling for deeper mechanistic studies and exploration into their translational relevance., (© 2024. The Author(s).)

Background: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently., Objective: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer., Methods: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate., Results: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up., Conclusions: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti 3 C 2 T X )-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H 2 O 2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H 2 O 2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10 -4 ng/mL to 1 × 10 5 ng/mL, accompanied by a low detection limit (1.6 × 10 -4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Resilience is considered as a protective factor that can assist individuals to reduce post-traumatic stress reactions. In recent years, armies in many countries have widely implemented resilience training programs before deployment to prevent or reduce post-deployment combat stress reactions. Therefore, this study aims to review what is known about resilience interventions for military personnel in pre deployment., Methods: Based on Arskey and O'Malley's framework, a scoping review was completed. This review was performed through searching databases including PubMed, Embase, Web of Science, Medline and the Cochrane Library, and screening literature to extract data, finally summarizing the findings., Results: A total of 25 studies focusing on resilience interventions for military personnel in pre deployment were involved and analyzed using intervention approaches, outcome measures, intervention effects, and so on., Conclusion: Based on the existing evidence in this review, it is cautiously believed that the resilience intervention program for military personnel before deployment is effective. However, there is no single effective best method even the same type intervention can make different effects in different situations and populations. Therefore, the population differences and context should be fully considered in constructing and implementing program to build military personnel resilience., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Sun et al.)

Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy., Objectives: This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration., Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020., Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan-Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity., Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p  = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p  = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002-1.981, p  = 0.049] and OS (HR = 1.720, 95% CI: 1.127-2.624, p  = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p  = 0.020) and 10-year (0.694 versus 0.532, p  = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p  = 0.026; OS: 96.77% versus 85.46%, p  = 0.007)., Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

In this work, a novel sandwich-type electrochemical aptasensor based on the dual signal amplification strategy of hemin/G-quadruplex and AuNPs-MoS 2 was designed and constructed, which realized the highly sensitive and specific detection of thrombin (TB). In this aptasensor, the 15-mer TB-binding aptamer (TBA-1) modified with thiol group was immobilized on the surface of AuNPs modified glassy carbon electrode (AuNPs/GCE) as capturing elements. Another thiol-modified 29-mer TB-binding aptamer (TBA-2) sequence containing G-quadruplex structure for hemin immobilization was designed. The formed hemin/G-quadruplex/TBA-2 sequence was further combined to the AuNPs decorated flower-like molybdenum disulfide (AuNPs-MoS 2 ) composite surface via Au-S bonds, acting the role of reporter probe. In presence of the target TB, the sandwich-type electrochemical aptamer detection system could be formed properly. With the assistance of the dual signal amplification of AuNPs-MoS 2 and hemin/G-quadruplex toward H 2 O 2 reduction, the sandwich-type electrochemical aptasensor was successfully constructed for sensitive detection of TB. The results demonstrate that the fabricated aptasensor displays a wide linear range of 1.0 × 10 -6  ∼ 10.0 nM with a low detection limit of 0.34 fM. This proposed aptasensor shows potential application in the detection of TB content in real biological samples with high sensitivity, selectivity, and reliability., 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 © 2023. Published by Elsevier B.V.)

Online rumors are widespread and difficult to identify, which bring serious harm to society and individuals. To effectively detect and govern online rumors, it is necessary to conduct in-depth semantic analysis and understand the content features of rumors. This paper proposes a TFI domain ontology construction method, which aims to achieve semantic parsing and reasoning of the rumor text content. This paper starts from the term layer, the frame layer, and the instance layer, and based on the reuse of the top-level ontology, the extraction of core literature content features, and the discovery of new concepts in the real corpus, obtains the core classes (five parent classes and 88 subclasses) of the rumor domain ontology and defines their concept hierarchy. Object properties and data properties are designed to describe relationships between entities or their features, and the instance layer is created according to the real rumor datasets. OWL language is used to encode the ontology, Protégé is used to visualize it, and SWRL rules and pellet reasoner are used to mine and verify implicit knowledge of the ontology, and judge the category of rumor text. This paper constructs a rumor domain ontology with high consistency and reliability., (© 2024. The Author(s).)

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li + transference number (T + ) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li + , resulting in a self-folded structure and high T + around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Å in LiFEA to 4.367 Å in LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li + , anions, and solvents, presenting new prospects for advanced LMBs., (© 2024 Wiley‐VCH GmbH.)

Background: Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension., Methods: The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60-80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes., Results: The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8-73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7-110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s -1 ·year -1vs. 36.7 cm·s -1 ·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70-80 years or with SBP <140 mmHg., Conclusion: Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension., Clinical Trial Registration: http://www.clinicaltrials.gov ; No. NCT03015311., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Rumor governance is an important guarantee for social stability and public safety. Based on the life cycle and crisis cycle model, this paper conducts a synergistic analysis of China's rumor governance policies and regulations and the core scientific research literature on rumor governance in WOS and CNKI. In this paper, we use the TF-IDF algorithm to count the word frequencies of 326 policy and regulation texts, the Jieba-RoBERTa-Kmeans model to cluster high-frequency keywords, and CiteSpace software and the LLR clustering algorithm are utilized to extract and cluster keywords from 391 documents in the WOS database and from 703 documents in the CNKI database. Based on the synergistic analysis of the life cycle model, it is found that the research on policies and regulations precedes the research on literature, and both are in the period of refinement.Based on the synergistic analysis using the co-occurrence comparison of subject terms in the crisis cycle model, it is found that there is a lack of research in the stages of prevention, monitoring, and governance, and this paper proposes the systematic governance mechanism and strategy for crisis resolution that conforms to the trend of life cycle evolution and is synergistic with policy and literature. This study has only selected Chinese policies and regulations, and the proposed governance strategies have not yet been verified in practice; future research can expand the scope and depth of the study and conduct empirical research and pilot projects., 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.)

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD., Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed., Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions., Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD., 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 Song, Liao, Liu, Chen, Wang, Zhou, Zhang and Li.)

Existing studies revealed high clonal diversity among Staphylococcus aureus bacteremia isolates, especially for methicillin-sensitive S. aureus (MSSA) strains. A 66-year-old male patient presenting with a widespread methicillin-sensitive Staphylococcus aureus (MSSA) infection, accompanied by concurrent carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection.To evaluate the evolution of the present isolate, whole genome sequencing and bioinformatics analysis were performed for all available MSSA isolates. This patient recovered eventually through drainage and antibiotics combination. Therefore, the virulence factors of MSSA, as the primary pathogenicity, led to widely disseminated infection. The appropriate initial treatment is a major concern after culture identification., Competing Interests: None.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 Author(s).)

Background: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp., Methods: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed., Results: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five β-lactamase genes (bla GOB , bla BlaB , bla CME , bla OXA , and bla TEM ) responsible for β-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (β-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms., Conclusion: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism., (© 2024. The Author(s).)

Objective: This study aimed to explore the relationship between the intake of vitamin C, vitamin E and β-carotene, and the risk of Parkinson's disease (PD)., Methods: Web of Science, Embase, PubMed, Cochrane library, CNKI, and WanFang databases were searched from inception to 29 August 2022 for observational studies reporting the odds ratios (ORs) or relative risks (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by Vitamin C/Vitamin E/β-carotene intake. Random-effects models, publication bias assessment, subgroup, sensitivity and dose-response analyses were performed, using.Stata version 12.0., Results: A total of 13 studies were included. There was no significant association between high-dose vitamin C intake and the risk of PD compared with low-dose vitamin C intake (RR = 0.98, 95%CI:0.89,1.08). Compared with low-dose intake, high-dose intake of vitamin E can prevent the risk of PD (RR = 0.87, 95%CI:0.77,0.99). Compared with lower β-carotene intake, there was a borderline non-significant correlation between higher intake and PD risk (RR = 0.91, 95%CI:0.82,1.01), and high dose β-carotene intake was found to be associated with a lower risk of PD in women (RR = 0.78, 95%CI:0.64,0.96)., Conclusion: This study shows that vitamin E intake can reduce the risk of PD and play a preventive role.

Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China., Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase., Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase ( KPC ) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-β-lactamase ( NDM ) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing., Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Terahertz cross correlation spectroscopy (THz-CCS) systems using broadband incoherent light as the pumping source have received increasing attention from researchers in recent years. However, a comprehensive and in-depth understanding of THz-CCS is still needed to obtain a detailed optimization scheme. Here we systematically investigate the influences of the detection parameters, light propagation process, and pump source on the CCS signals. The impacts of the filter slopes and time constants in lock-in detection are revealed for optimizing the signal-to-noise ratio and bandwidth of the THz signal. By varying the optical fiber length and dispersion coefficient, the dispersion insensitivity of THz-CCS was experimentally demonstrated. The comparison of different pump sources (SLD and ASE) shows that the over-wide and non-flat pump spectrum may attenuate the CCS signal because of the energy waste brought by the photomixing process under the limited bandwidth of the photomixer. Our research may lead to a deeper understanding and further optimization of the THz-CCS system, which will promote the development and widespread application of what is to the best of our knowledge a new technique.

Danmakus are user-generated comments that overlay on videos, enabling real-time interactions between viewers and video content. The emotional orientation of danmakus can reflect the attitudes and opinions of viewers on video segments, which can help video platforms optimize video content recommendation and evaluate users' abnormal emotion levels. Aiming at the problems of low transferability of traditional sentiment analysis methods in the danmaku domain, low accuracy of danmaku text segmentation, poor consistency of sentiment annotation, and insufficient semantic feature extraction, this paper proposes a video danmaku sentiment analysis method based on MIBE-RoBERTa-FF-BiLSTM. This paper constructs a "Bilibili Must-Watch List and Top Video Danmaku Sentiment Dataset" by ourselves, covering 10,000 positive and negative sentiment danmaku texts of 18 themes. A new word recognition algorithm based on mutual information (MI) and branch entropy (BE) is used to discover 2610 irregular network popular new words from trigrams to heptagrams in the dataset, forming a domain lexicon. The Maslow's hierarchy of needs theory is applied to guide the consistent sentiment annotation. The domain lexicon is integrated into the feature fusion layer of the RoBERTa-FF-BiLSTM model to fully learn the semantic features of word information, character information, and context information of danmaku texts and perform sentiment classification. Comparative experiments on the dataset show that the model proposed in this paper has the best comprehensive performance among the mainstream models for video danmaku text sentiment classification, with an F1 value of 94.06%, and its accuracy and robustness are also better than other models. The limitations of this paper are that the construction of the domain lexicon still requires manual participation and review, the semantic information of danmaku video content and the positive case preference are ignored., (© 2024. The Author(s).)

To facilitate accurate prediction and empirical research on regional agricultural carbon emissions, this paper uses the LLE-PSO-XGBoost carbon emission model, which combines the Local Linear Embedding (LLE), Particle Swarm Algorithm (PSO) and Extreme Gradient Boosting Algorithm (XGBoost), to forecast regional agricultural carbon emissions in Anhui Province under different scenarios. The results show that the regional agricultural carbon emissions in Anhui Province generally show an upward and then downward trend during 2000-2021, and the regional agricultural carbon emissions in Anhui Province in 2030 are expected to fluctuate between 11,342,100 tones and 14,445,700 tones under five different set scenarios. The projections of regional agricultural carbon emissions can play an important role in supporting the development of local regional agriculture, helping to guide the input and policy guidance of local rural low-carbon agriculture and promoting the development of rural areas towards a resource-saving and environment-friendly society., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Qi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A ( pspA ) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA . Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA . This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase., Competing Interests: The authors declare no conflict of interest.

Background: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown., Methods: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo., Results: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N 6 -methyladenosine (m 6 A) modification orchestrated efficient initiation of circ-YAP translation, requiring m 6 A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop., Conclusions: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis., (© 2023. The Author(s).)

Purpose: To determine the accuracy of manual compass measurement and trigonometric determination of proptosis (MCMATDP)., Methods: This agreement study included 120 eyes without eye diseases or injury of 60 patients who visited the ophthalmic clinic of Peking University Shenzhen Hospital from February 2020 to June 2020. The absolute values of proptosis were measured by MCMATDP and computed tomography (CT). The differences between the two methods were shown by Bland-Altman plot., Results: The cohort comprised 25 males and 35 females (average age 38.3 years). The absolute value of proptosis measured by CT was correlated with the MCMATDP. Further analysis showed that a 95% limit of agreement (LoA) was - 0.53 to 0.60 mm in the right eye and - 0.46 to 0.55 mm in the left eye between CT and MCMATDP. In addition, the 95% LoA was - 0.49 to 0.60 mm in both eyes between the two methods. All points were < 5% in Bland-Altman plots., Conclusions: Compared to CT, MCMATDP is rather consistent in proptosis measurement. The new method is feasible in clinical practice when measuring proptosis. With the development of non-contact intelligent measurement software and the continuous improvement in measurement accuracy, a non-invasive, simple, and inexpensive measurement mode is true based on the theory of MCMATDP., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Artificially designed modulators that enable a wealth of freedom in manipulating the terahertz (THz) waves at will are an essential component in THz sources and their widespread applications. Dynamically controlled metasurfaces, being multifunctional, ultrafast, integrable, broadband, high contrasting, and scalable on the operating wavelength, are critical in developing state-of-the-art THz modulators. Recently, external stimuli-triggered THz metasurfaces integrated with functional media have been extensively explored. The vanadium dioxide (VO 2 )-based hybrid metasurfaces, as a unique path toward active meta-devices, feature an insulator-metal phase transition under the excitation of heat, electricity, and light, etc. During the phase transition, the optical and electrical properties of the VO 2 film undergo a massive modification with either a boosted or dropped conductivity by more than four orders of magnitude. Being benefited from the phase transition effect, the electromagnetic response of the VO 2 -based metasufaces can be actively controlled by applying external excitation. In this review, we present recent advances in dynamically controlled THz metasurfaces exploiting the VO 2 phase transition categorized according to the external stimuli. THz time-domain spectroscopy is introduced as an indispensable platform in the studies of functional VO 2 films. In each type of external excitation, four design strategies are employed to realize external stimuli-triggered VO 2 -based THz metasurfaces, including switching the transreflective operation mode, controlling the dielectric environment of metallic microstructures, tailoring the equivalent resonant microstructures, and modifying the electromagnetic properties of the VO 2 unit cells. The microstructures' design and electromagnetic responses of the resulting active metasurfaces have been systematically demonstrated, with a particular focus on the critical role of the VO 2 films in the dynamic modulation processes.

Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients., (© 2023. The Author(s).)

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies., Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691., Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported., Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients., Funding: The study was supported by Hansoh Medical Development Group., Competing Interests: All authors declare that they have no conflict of interest., (© 2023 The Authors.)

The aim of this study was to comprehensively evaluate metagenomic next-generation sequencing (mNGS), Acid-fast bacillus stain (AFB), MGIT960 culture, polymerase-chain-reaction (PCR), and Xpert MTB/RIF in the diagnosis of tuberculous meningitis (TBM). A cohort of 280 patients who presented with suspected TBM (ie, headache or altered mental status with clinical signs of meningism) were analyzed. The sensitivities of the 5 assays for the diagnosis of TBM ranged from 10.0% to 70.0%. The AFB had the lowest sensitivity of 10.0% (0.5-45.9), while mNGS and PCR had the highest sensitivity, both at 70.0% (35.4-91.9). mNGS demonstrated a distinct advantage in identifying a wider array of pathogens, including viruses, in CSF samples. PCR was a cost-effective option with excellent sensitivity and specificity. However, no single method was statistically significantly better than any other in the diagnosis of TBM. New diagnostic techniques are urgently needed for the independent, rapid and accurate detection of Mycobacterium tuberculosis to guide the diagnosis of TBM., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Clear cell renal cell carcinoma (CCRCC) is a common tumor of the urological system for which surgery is the preferred treatment, but there is a lack of therapeutic options after surgery. This study aims to explore the biological role of GNG7 on CCRCC from a genetic perspective. Differences in mRNA expression and patient survival of GNG7 in patients with CCRCC and healthy patients were analyzed using the TCGA database. It was observed that GNG7 gene expression was downregulated in CCRCC tissue compared with healthy tissue, and high GNG7 predicted better prognosis for patients, and GNG7 also showed strong variability in clinical and TMN staging. The immune relevance of GNG7 and related genes was explored using renal cancer data from CCLE and TISIDB database. It was verified that the risk score constructed by 7 GNG7-related regulators might be used as an independent prognostic risk factor for CCRCC. A CCRCC prognostic model that involved 7 immune genes was further established to predict the survival probabilities of patients. At last, the GEO database and immunochemical tissue staining were used to validate GNG7 expression in CCRCC. Our study proposed a novel panel of genes to predict CCRCC OS based on GNG7-related immune genes, which may help to accurately predict the prognosis of CCRCC patients and make better clinical decisions for individual treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The low reversibility of Li deposition/stripping in conventional carbonate electrolytes hinders the development of lithium metal batteries. Herein, we proposed a combination of solvents with a moderate donor number (DN) and LiNO 3 as the sole salt, which has rarely been attempted due to its low solubility or dissociation degree in common solvents. It is found that the DN value of solvents is highly correlated to the reversibility of Li deposition behavior when LiNO 3 is applied as the sole salt. The combination of LiNO 3 and solvents with moderate DN behaves like a quasi-concentrated electrolyte even at a common or moderate concentration, while neither the solvents with poor solubility and low dissociation for LiNO 3 (which usually corresponds to a low DN) nor the solvents with high dissociation for LiNO 3 (which usually corresponds to an overly high DN) can achieve a high reversibility for low conductivity or excessive solvent decomposition. As a result, a Coulombic efficiency as high as 99.6% for Li deposition/stripping is achieved with the optimized combination. We believe this work will give a better understanding of the role of anions and solvents in the regulation of the solvation structure, and DN can be utilized as an important guideline to sieve suitable solvents for LiNO 3 as the main salt to exhibit intriguing properties beyond traditional cognition.

Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin-dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin-resistant cells and tissues due to the loss of N6-methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient-derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl-CoA synthetase long-chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron-dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin-resistant CRC., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The utilization of Co-Cr-Fe-based black pigments bears considerable significance within the realm of commercial ceramic pigments, owing to their distinctive spinel structure, remarkable high-temperature stability, and exceptional chromatic attributes. This study delves into the synthesis of diverse black pigment configurations by employing the co-precipitation method, leveraging the interplay of these three metallic oxides. This investigation encompasses a comprehensive scrutiny of ion valences, crystal structures and parameters, colorimetric properties, and their interrelationships. The methodology integrates the response surface methodology (RSM) framework, using theoretical formulations to navigate the material ratios and elucidating the associations between the resultant compositions and color coordinate values, aligned with the CIE- Lab * colorimetric methodology. The derived predictive models yielded an optimized black pigment composition, characterized by heightened black intensity and a refined formulation.

Background: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory., Results: Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results., Conclusions: The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels., Methods: The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function., Results: In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg., Conclusions: Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension., Registration: ClinicalTrials.gov: NCT03015311., Competing Interests: Conflict of interest: Olmesartan medoxomil tablets were donated by Nanjing Chia Tai Tianqing Pharmaceutical Co. Ltd., Nanjing, China. Amlodipine besylate tablets were donated by China Resources Saike Pharmaceutical Co. Ltd., Beijing, China. BP monitors were donated by Omron Healthcare Co. Ltd. The companies that donated the drugs and devices had no role in the design of the study or the analysis of the data. All authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: In urban road scenes, due to the small size of traffic signs and the large amount of surrounding interference information, current methods are difficult to achieve good detection results in the field of unmanned driving., Methods: To address the aforementioned challenges, this paper proposes an improved E-YOLOv4-tiny based on the YOLOv4-tiny. Firstly, this article constructs an efficient layer aggregation lightweight block with deep separable convolutions to enhance the feature extraction ability of the backbone. Secondly, this paper presents a feature fusion refinement module aimed at fully integrating multi-scale features. Moreover, this module incorporates our proposed efficient coordinate attention for refining interference information during feature transfer. Finally, this article proposes an improved S-RFB to add contextual feature information to the network, further enhancing the accuracy of traffic sign detection., Results and Discussion: The method in this paper is tested on the CCTSDB dataset and the Tsinghua-Tencent 100K dataset. The experimental results show that the proposed method outperforms the original YOLOv4-tiny in traffic sign detection with 3.76% and 7.37% improvement in mAP, respectively, and 21% reduction in the number of parameters. Compared with other advanced methods, the method proposed in this paper achieves a better balance between accuracy, real-time performance, and the number of model parameters, which has better application value., 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 Xiao, Yin, Cui, Zhang, Yao and Fang.)

Leukemia is a group of highly heterogeneous and life-threatening blood cancers that originate from abnormal hematopoietic stem cells. Multiple treatments are approved for leukemia, including chemotherapy, targeted therapy, hematopoietic stem cell transplantation, radiation therapy, and immunotherapy. Unfortunately, therapeutic resistance occurs in a substantial proportion of patients and greatly compromises the treatment efficacy of leukemia, resulting in relapse and mortality. The abnormal activity of receptor tyrosine kinases, cell membrane transporters, intracellular signal transducers, transcription factors, and anti-apoptotic proteins have been shown to contribute to the emergence of therapeutic resistance. Despite these findings, the exact mechanisms of treatment resistance are still not fully understood, which limits the development of effective measures to overcome it. Long non-coding RNAs (lncRNA) are a class of regulatory molecules that are gaining increasing attention, and lncRNA-mediated regulation of therapeutic resistance against multiple drugs for leukemia is being revealed. These dysregulated lncRNAs not only serve as potential targets to reduce resistance but also might improve treatment response prediction and individualized treatment decision. Here, we summarize the recent findings on lncRNA-mediated regulation of therapeutic resistance in leukemia and discuss future perspectives on how to make use of the dysregulated lncRNAs in leukemia to improve treatment outcome., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA)., Methods: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models., Results: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 μM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA., Conclusion: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment., (© 2023 Wiley Periodicals LLC.)

Owing to their biocompatibility, chemical stability, film-forming ability, cost-effectiveness, and excellent electroactive properties, poly(vinylidene fluoride) (PVDF) and PVDF-based polymers are widely used in sensors, actuators, energy harvesters, etc. In this review, the recent research progress on the PVDF phase structures and identification of different phases is outlined. Several approaches for obtaining the electroactive phase of PVDF and preparing PVDF-based nanocomposites are described. Furthermore, the potential applications of these materials in wearable sensors and human energy harvesters are discussed. Finally, some challenges and perspectives for improving the properties and boosting the applications of these materials are presented.

Objectives: Regulation of microglia polarisation may be a new way to treat ischaemic stroke based on its effects on brain injury. Isoliquiritigenin (ILG) is a flavonoid with neuroprotective function. The study investigated whether ILG regulated microglial polarisation and affects brain injury., Methods: Here, a transient middle cerebral artery occlusion (tMCAO) model in vivo and lipopolysaccharide (LPS)-induced BV2 cells in vitro were established. Brain damage was assessed using a 2,3,5-triphenyl-tetrazolium-chloride staining assay. Microglial polarisation was analysed using enzyme linked immunosorbent assay, quantitative real-time polymerase chain reaction, and immunofluorescence assay. The levels of p38/MAPK pathway-related factors were measured by western blot., Key Findings: ILG suppressed infarct volume and neurological function of tMCAO rats. Moreover, ILG facilitated M2 microglia polarisation and suppressed M1 polarisation in the tMCAO model and LPS-induced BV2 cells. Moreover, ILG reduced the phosphorylation of p38, MAPK activated protein kinase 2, and heat shock protein 27 induced by LPS. Rescue study showed that activating the p38/MAPK pathway reversed the microglia polarisation induced by ILG and inactivating the p38/MAPK pathway enchanced the microglia polarisation., Conclusion: ILG promoted microglia M2 polarisation by inactivating the p38/MAPK pathway, suggesting that ILG has the potential for the treatment of ischaemic stroke., (© Crown copyright 2023.)

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β = 0.041, p = 0.01) and lower levels of serum creatinine (β = -0.068, p = 0.001) and serum uric acid (β = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

In this work, GHz and THz complex dielectric spectra of a polyethylene glycol dimethyl ether (2000 g/mol) aqueous solution were studied. The reorientation relaxation of water in this kind of macro-amphiphilic molecule solution can be well described by three Debye models, including under-coordinated water, bulk-like water [water molecules in a tetrahedral hydrogen bond network (bulk water) and bulk water molecules affected by hydrophobic groups], and slow hydrating water (water molecules donating hydrogen bonds to hydrophilic ether groups). The reorientation relaxation timescales of bulk-like water and slow hydration water both show increases with concentration from 9.8 to 26.7 ps and from 46.9 to 100.1 ps, respectively. By estimating the ratios of the dipole moment of slow hydration water to the dipole moment of bulk-like water, we calculated the experimental Kirkwood factors of bulk-like and slow hydrating water. The experimental Kirkwood factor of bulk-like water increased from 3.17 to 3.44 with concentrations, while the experimental Kirkwood factor of slow hydrating water roughly remained constant at 4.13 from concentrations of 15%-60%. The estimated water molecule numbers of three water components around monomers also confirm our sorting for water components., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

In battery electrolyte design principles, tuning Li + solvation structure is an effective way to connect electrolyte chemistry with interfacial chemistry. Although recent proposed solvation tuning strategies are able to improve battery cyclability, a comprehensive strategy for electrolyte design remains imperative. Here, we report a solvation tuning strategy by utilizing molecular steric effect to create a "bulky coordinating" structure. Based on this strategy, the designed electrolyte generates an inorganic-rich solid electrolyte interphase (SEI) and cathode-electrolyte interphase (CEI), leading to excellent compatibility with both Li metal anodes and high-voltage cathodes. Under an ultrahigh voltage of 4.6 V, Li/NMC811 full-cells ( N / P = 2.0) hold an 84.1% capacity retention over 150 cycles and industrial Li/NMC811 pouch cells realize an energy density of 495 Wh kg -1 . This study provides innovative insights into Li + solvation tuning for electrolyte engineering and offers a promising path toward developing high-energy Li metal batteries.

The establishment of abundant three-phase interfaces with accelerated mass transfer in air cathodes is highly desirable for the development of high-rate and long-cycling rechargeable zinc-air batteries (ZABs). Covalent organic frameworks (COFs) exhibit tailored nanopore structures, facilitating the rational tuning of their specific properties. Here, by finely tuning the fluorinated nanopores of a COF, a novel air cathode for rechargeable ZABs is unprecedentedly designed and synthesized. COF nanosheets are decorated with fluorinated alkyl chains, which shows high affinity to oxygen (O 2 ), in its nanopores (fluorinated COF). The fluorinated COF nanosheets are stacked into well-defined O 2 -transport channels, which are then assembled into aerophilic "nano-islands" on the hydrophilic FeNi layered-double-hydroxide (FeNi LDH) electrocatalyst surface. Therefore, the mass-transport "highway" for O 2 and water is segregated on the nanoscale, which significantly enlarges the area of three-phase boundaries and greatly promotes the mass-transfer therein. ZABs based on the COF-modified air cathode deliver a small charge/discharge voltage gap (0.64 V at 5 mA cm -2 ), a peak power density (118 mW cm -2 ), and a stable cyclability. This work provides a feasible approach for the design of the air cathodes for high-performance ZABs, and will expand the new application of COFs., (© 2023 Wiley-VCH GmbH.)

Lithium (Li)-metal batteries (LMBs) with stable solid electrolyte interphase (SEI) and dendrite-free formation have great potential in next-generation energy storage devices. Here, vertically aligned 3D Cu 2 S nanosheet arrays are fabricated on the surface of commercial Cu foils, which in situ generate ultrathin Cu nanosheet arrays to reduce local current density and Li 2 S layers on the surfaces to work as an excellent artificial SEI. It is found that Li presents a 3D-to-planar deposition model, and Li 2 S layers are reversibly movable between the 3D nanosheet surface and 2D planar surface of Li during long-term cycling. This enables ultrasmooth and dense Li deposition at 1 mA cm -2 , presenting an average thickness of ≈53.0 µm at 10 mAh cm -2 , which is close to the theoretical Li foil thickness and is highly reversible at different cycles. Thus, 1150 stable cycles with high Coulombic efficiency (CE, 99.1%) at ether-based electrolytes and 300 stable cycles with high CE (98.8%) at carbonate electrolytes are realized in half-cell with a capacity of 1 mAh cm -2 at 1 mA cm -2 . When coupled with commercial cathodes (LiFePO 4 or LiNi 0.8 Co 0.1 Mn 0.1 O 2 ), the full cells present substantially enhanced cyclability under high cathode loading, limited (or zero) Li excess, and lean electrolyte conditions, even at -20 °C., (© 2023 Wiley-VCH GmbH.)

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo . In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects., 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 Xiao, Wu, Dai, Zhang and Cao.)

Background: The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response. Methods: A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24 years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined. The dual-luciferase assay was carried out to assess the effect of genetic variants on gene transcriptional activity. Results: The variant rs11039149A>G in the promoter of nuclear receptor subfamily 1 group H member 3 ( NR1H3 ) was associated with the change in systolic blood pressure (ΔSBP) in response to calcium channel blockers (CCBs) monotherapy. Patients carrying rs11039149AG genotype showed a significant increase of systolic blood pressure (SBP) at follow-up compared with AA carriers, and the difference of ΔSBP between AG and AA carriers was 5.94 mm Hg (95%CI: 2.09-9.78, p = 0.002). In 1,184 patients with CCBs therapy, SBP levels decreased in AA carriers, but increased in AG carriers, the difference of ΔSBP between AG and AA carriers was 8.04 mm Hg (95%CI: 3.28-12.81, p = 0.001). Further analysis in 359 patients with CCBs monotherapy, the difference of ΔSBP between AG and AA carriers was 15.25 mm Hg (95%CI: 6.48-24.02, p = 0.001). However, there was no significant difference in ΔSBP between AG and AA carriers with CCBs multitherapy. The rs11039149A>G was not associated with the cardiovascular events incidence during the follow-up. Additionally, transcriptional factor forkhead box C1 ( FOXC1 ) bound to the NR1H3 promoter containing rs11039149A and significantly increased the transcriptional activity, while rs11039149 A to G change led to a loss-of-function and disabled FOXC1 binding. For the other 10 variants, associations with blood pressure changes or risk of cardiovascular events were not observed. Conclusion: Hypertensive patients with rs11039149AG genotype in the NR1H3 gene have a significant worse SBP control in response to CCBs monotherapy compared with AA carriers. Our findings suggest that the NR1H3 gene might act as a promising genetic factor to affect individual sensitivity to antihypertensive drugs., 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 Chen, Han, Wu, Hui, Yang, Zhong, Zhang and Zhang.)