Incidence, antimicrobial resistance and mortality of Klebsiella pneumoniae bacteraemia in Shanghai, China, 2018-2022.

BACKGROUND: Klebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). OBJECTIVES: To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China. METHODS: A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality. RESULTS: A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality. CONCLUSION: MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk.

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer characterized by metabolic reprogramming. Glutamine metabolism is pivotal in metabolic reprogramming, contributing to the significant heterogeneity observed in ccRCC. Consequently, developing prognostic markers associated with glutamine metabolism could enhance personalized treatment strategies for ccRCC patients. This study obtained RNA sequencing and clinical data from 763 ccRCC cases sourced from multiple databases. Consensus clustering of 74 glutamine metabolism related genes (GMRGs)- profiles stratified the patients into three clusters, each of which exhibited distinct prognosis, tumor microenvironment, and biological characteristics. Then, six genes (SMTNL2, MIOX, TMEM27, SLC16A12, HRH2, and SAA1) were identified by machine-learning algorithms to develop a predictive signature related to glutamine metabolism, termed as GMRScore. The GMRScore showed significant differences in clinical prognosis, expression profile of immune checkpoints, abundance of immune cells, and immunotherapy response of ccRCC patients. Besides, the nomogram incorporating the GMRScore and clinical features showed strong predictive performance in prognosis of ccRCC patients. ALDH18A1, one of the GRMGs, exhibited elevated expression level in ccRCC and was related to markedly poorer prognosis in the integrated cohort, validated by proteomic profiling of 232 ccRCC samples from Fudan University Shanghai Cancer Center (FUSCC). Conducting western blotting, CCK-8, transwell, and flow cytometry assays, we found the knockdown of ALDH18A1 in ccRCC significantly promoted apoptosis and inhibited proliferation, invasion, and epithelial-mesenchymal transition (EMT) in two human ccRCC cell lines (786-O and 769-P). In conclusion, we developed a glutamine metabolism-related prognostic signature in ccRCC, which is tightly linked to the tumor immune microenvironment and immunotherapy response, potentially facilitating precision therapy for ccRCC patients. Additionally, this study revealed the key role of ALDH18A1 in promoting ccRCC progression for the first time.

Recycling and Reuse of Spent LIBs: Technological Advances and Future Directions.

Recovering valuable metals from spent lithium-ion batteries (LIBs), a kind of solid waste with high pollution and high-value potential, is very important. In recent years, the extraction of valuable metals from the cathodes of spent LIBs and cathode regeneration technology are still rapidly developing (such as flash Joule heating technology to regenerate cathodes). This review summarized the studies published in the recent ten years to catch the rapid pace of development in this field. The development, structure, and working principle of LIBs were firstly introduced. Subsequently, the recent developments in mechanisms and processes of pyrometallurgy and hydrometallurgy for extracting valuable metals and cathode regeneration were summarized. The commonly used processes, products, and efficiencies for the recycling of nickel-cobalt-manganese cathodes (NCM/LCO/LMO/NCA) and lithium iron phosphate (LFP) cathodes were analyzed and compared. Compared with pyrometallurgy and hydrometallurgy, the regeneration method was a method with a higher resource utilization rate, which has more industrial application prospects. Finally, this paper pointed out the shortcomings of the current research and put forward some suggestions for the recovery and reuse of spent lithium-ion battery cathodes in the future.

The mediating effect of job embeddedness on the nursing work environment and transition shock among new nurses: A cross-sectional study.

AIMS: This study aims to investigate the status of transition shock and test the mediating effect of job embeddedness on the nursing work environment and transition shock among new nurses. BACKGROUND: Transition shock, primarily experienced during the first two years of employment, manifests itself as an unsettling or discordant experience among new nurses, which is caused by the gap between theoretical learning and clinical practice. DESIGN: This is a cross-sectional survey study, following the STROBE guidelines. METHODS: A cross-sectional study was conducted among 435 new nurses from November to December 2022 in Hunan Province, China. The participants were recruited to complete a sociodemographic information questionnaire and rank 3 standardized scales of transition shock (Cronbach's alpha = 0.918), job embeddedness (Cronbach's alpha = 0.890) and nursing work environment (Cronbach's alpha = 0.946). Then, the data were analysed by SPSS 26.0 and mediation testing was performed using Hayes' PROCESS macro (Model 4). A p value of < 0.05 was deemed statistically significant. RESULTS: The mean score with standard deviation of the transition shock scale in new nurses was 88.86 (22.50). The place of origin, working months and weekly working hours were the significant sociodemographic factors that affected the transition shock score in new nurses. Transition shock was found to be negatively related to both job embeddedness (r = -0.468, p < 0.001) and nursing work environment (r = -0.416, p < 0.001), while job embeddedness mediated the relationship between transition shock and nursing work environment (R2 = 0.262, F = 30.455, p < 0.001). CONCLUSIONS: New nurses from rural areas and with longer weekly working hours are more prone to transition shock. Those with 6-12 months of employment experience more pronounced transition shock than those with less than 6 months. In addition, the nursing work environment can not only directly influence transition shock for new nurses but also indirectly influence it through job embeddedness. These findings provide a basis for hospitals to develop strategies to effectively address transition shock in new nurses and ultimately solve the nursing shortage issue.

Lanthanide coordination polymers@CuO nanoparticles: Enhanced self-cascade nanoenzyme activity and ratiometric fluorescence assay of glutathione.

Tandem enzyme can catalyze some cascade reactions with high efficiency, and some few tandem enzyme-like mimics have been discovered recently. Further improving the catalytic efficiency of tandem nanoenzymes with facile method may undoubtedly promote and broaden their applications in various fields. In this work, cupric oxide nanoparticles (CuO NPs) with dual-functional enzyme mimics were synthesized using the rapid deposition method in advance, which simultaneously combined with lanthanide infinite coordination polymers (Ln ICPs) during the self-assemble of Tb3+, guanine-5'-triphosphate (GTP) and auxiliary ligand terephthalic acid (TA). Excitingly, the obtained Tb-GTP/TA@CuO ICPs, not only displayed obviously enhanced tandem catalytic activity compared with pure CuO NPs, but also provided a versatile ratiometric platform for ultrahigh selective and sensitive detection of glutathione (GSH) under single-wavelength excitation. A good linear relationship between the ratio signal and the GSH concentration was spanning from 0.001 to 20 µM with an impressive detection limit of 0.50 nM. This study opens a new and universal avenue for preparing integrated multifunctional probes by coupling of nanoenzyme catalytic activity with superior luminescent Ln ICPs through facile method.

EGCG induces degradation of active folate in serum via H2O2 generation, while L-ascorbic acid effectively reverses this effect.

Empirical studies have indicated that excessive tea consumption may potentially decrease folate levels within the human body. The main active component in green tea, epigallocatechin gallate (EGCG), significantly reduces the concentration of 5-methyltetrahydrofolate (5-MTHF) in both solution and serum. However, our findings also demonstrate that the pro-degradation effect of EGCG on 5-MTHF can be reversed by L-ascorbic acid (AA). Subsequent investigations suggest that EGCG could potentially expedite the degradation of 5-MTHF by generating hydrogen peroxide. In summary, excessive tea intake may lead to reduced folate levels in the bloodstream, yet timely supplementation of AA could potentially safeguard folate from degradation.

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.

BACKGROUND: Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. METHODS: We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. RESULTS: Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). CONCLUSION: The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

The frontier of tungsten oxide nanostructures in electronic applications.

Electrochromic (EC) glazing has garnered significant attention recently as a crucial solution for enhancing energy efficiency in future construction and automotive sectors. EC glazing could significantly reduce the energy usage of buildings compared to traditional blinds and glazing. Despite their commercial availability, several challenges remain, including issues with switching time, leakage of electrolytes, production costs, etc. Consequently, these areas demand more attention and further studies. Among inorganic-based EC materials, tungsten oxide nanostructures are essential due to its outstanding advantages such as low voltage demand, high coloration coefficient, large optical modulation range, and stability. This review will summarize the principal design and mechanism of EC device fabrication. It will highlight the current gaps in understanding the mechanism of EC theory, discuss the progress in material development for EC glazing, including various solutions for improving EC materials, and finally, introduce the latest advancements in photo-EC devices that integrate photovoltaic and EC technologies.

The role of the nursing work environment, head nurse leadership and presenteeism in job embeddedness among new nurses: a cross-sectional multicentre study.

BACKGROUND: The retention of new nurses has become a major challenge for medical institutions. Job embeddedness has been seen as a valuable lens for examining nurse turnover, but greater details about job embeddedness are rarely disclosed, especially among new nurses. This study aimed to reveal how the nursing work environment, head nurse leadership and presenteeism shape job embeddedness in this population from the perspective of conservation of resources (COR) theory. METHOD: A cross-sectional multicentre study involving 436 participants from 10 cities and 33 hospitals was conducted over 4 months. Samples were selected using a two-stage convenience sampling method. A sequential multiple mediation model performed with SPSS-PROCESS was used to analyse the relationships among the nursing work environment, head nurse leadership, presenteeism and job embeddedness. RESULTS: The nursing work environment not only directly affects the job embeddedness of new nurses (ß = 0.480, p < 0.001) but also indirectly affects it through the sequential multiple mediating effects of head nurse leadership and presenteeism (R2 = 0.535, F = 82.160, p < 0.001). CONCLUSIONS: New nurses' job embeddedness needs to be improved. These results suggest that preserving adequate resources for new nurses, such as work environment resources, head nurse leadership resources, and individual productivity resources, is an effective way to shape their job embeddedness. In addition, when a certain resource is insufficient, fully considering the principles of investment and buffering between resources and providing reciprocal, alternative, or buffer resources in a timely manner are necessary to improve new nurses' job embeddedness. LARGE LANGUAGE MODELS: Large language models (LLMs), such as ChatGPT, were not used during the writing of this article. An expert native English speaker performed language revision.

Isorhamnetin suppresses the epithelial-mesenchymal transition of the retinal pigment epithelium both in vivo and in vitro through Nrf2-dependent AKT/GSK-3ß pathway.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly worldwide. Multiple studies have shown that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of AMD. Isorhamnetin (Isor) is a flavonoid compound that inhibits EMT in tumor cells. However, whether it can also attenuate EMT in the retinal pigment epithelium (RPE) is unknown. Therefore, our study was designed to probe the possible impact of Isor on EMT process in both mouse retina and ARPE-19 cells. C57BL/6 mice were utilized to establish a dry AMD model. Isor and LCZ (a mixture of luteine/ß-carotene/zinc gluconate) were administered orally for 3 months. The effects of Isor on the retina were evaluated using fundus autofluorescence, optical coherence tomography, and transmission electron microscopy. Transwell and wound healing assay were employed to assess ARPE-19 cell migration. Western blotting and immunofluorescence were used to measure the protein expressions associated with EMT, Nrf2 and AKT/GSK-3ß pathway. The findings indicated that Isor alleviated dry AMD-like pathological changes in vehicle mice retina, inhibited the migration of Ox-LDL-treated ARPE-19 cells, and repressed the EMT processes in vivo and in vitro. Furthermore, Isor activated Nrf2 pathway and deactivated AKT/GSK-3ß pathway in both vehicle mice and ARPE-19 cells. Interestingly, when Nrf2 siRNA was transfected into ARPE-19 cells, the inhibitory effect of Isor on EMT and AKT/GSK-3ß pathway was attenuated. These results suggested that Isor inhibited EMT processes via Nrf2-dependent AKT/GSK-3ß pathway and is a promising candidate for dry AMD treatment.

Transition readiness of adolescents with cancer: A cross-sectional study based on self-determination theory.

PURPOSE: This study aimed to assess the transition readiness of adolescents with cancer in central China and to explore the paths associated with transition readiness based on self-determination theory (SDT). METHODS: Self-management and transition to adulthood with Rx = treatment questionnaire, patient activation measure, perceived social support scale and general self-efficacy scale were used to measure transition readiness as well as constructs pertaining to SDT (competence, relatedness and autonomy). The factors influencing transition readiness were evaluated using multiple linear regression. Models 4 and 6 in PROCESS Macro 3.3 were used to test the mediating effects and chain mediating effects, respectively. RESULTS: A total of 217 adolescents with cancer were included; their mean transition readiness score was 59.95 (11.34). Age (t = 6.086, p < 0.000), duration of diagnosis (t = 2.218, p = 0.028), completion of treatment (t = -2.036, p = 0.043), insurance, and competence (t = 11.149, p < 0.000) were significantly associated with transition readiness. The direct effects of self-efficacy and perceived social support on transition readiness were not significant. However, two chain mediating paths were observed: perceived social support - self-efficacy - patient activation - transition readiness and self-efficacy - perceived social support - patient activation - transition readiness; the effect values of these paths were 0.0678 and 0.0703, respectively. CONCLUSIONS: The findings of this study add to the evidence supporting the use of SDT-related constructs to promote transition readiness among adolescents with cancer, highlight the importance of encouraging patient activation, and clarify the ancillary roles of social support and self-efficacy in patient activation development during transitional period.

Circulating leptin levels in the assessment of Crohn’s disease activity and its relation to nutritional status / Los niveles circulantes de leptina en la evaluación de la actividad de la enfermedad de Crohn y su relación con el estado nutricional

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn’s disease (CD).Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessedusing the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included bodymass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs.Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,48 ± 1,222 ng/ml). Significant differences were seenin NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGAscores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showedassociation between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD.Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional toolfor evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improvenutritional status.(AU)

Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC).Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricionalse evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Losindicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, elgrosor del pliegue cutáneo del tríceps y la circunferencia de las piernas.Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.48 ± 1.222 ng/ml). Se obser-varon diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativasentre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales.La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml comoumbral para EC.Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC. La leptinapuede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.(AU)

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial.

Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE). Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation. Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group. Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863.

Protective Role of Electroacupuncture Against Cognitive Impairment in Neurological Diseases.

Many neurological diseases can lead to cognitive impairment in patients, which includes dementia and mild cognitive impairment and thus create a heavy burden both to their families and public health. Due to the limited effectiveness of medications in treating cognitive impairment, it is imperative to develop alternative treatments. Electroacupuncture (EA), a required method for Traditional Chinese Medicine, has the potential treatment of cognitive impairment. However, the molecular mechanisms involved have not been fully elucidated. Considering the current research status, preclinical literature published within the ten years until October 2022 was systematically searched through PubMed, Web of Science, MEDLINE, Ovid, and Embase. By reading the titles and abstracts, a total of 56 studies were initially included. It is concluded that EA can effectively ameliorate cognitive impairment in preclinical research of neurological diseases and induce potentially beneficial changes in molecular pathways, including Alzheimer's disease, vascular cognitive impairment, chronic pain, and Parkinson's disease. Moreover, EA exerts beneficial effects through the same or diverse mechanisms for different disease types, including but not limited to neuroinflammation, neuronal apoptosis, neurogenesis, synaptic plasticity, and autophagy. However, these findings raise further questions that need to be elucidated. Overall, EA therapy for cognitive impairment is an area with great promise, even though more research regarding its detailed mechanisms is warranted.

Jun/Fos promotes migration and invasion of hepatocellular carcinoma cells by enhancing BORIS promoter activity.

The Brother of the Regulator of Imprinted Sites (BORIS), as a specific indicator of hepatocellular carcinoma, exhibits a significant increase in expression. However, its upstream regulatory network remains enigmatic. Previous research has indicated a strong correlation between the Hippo pathway and the progression of hepatocellular carcinoma. It is well established that the Activator Protein-1 (AP-1) frequently engages in interactions with the Hippo pathway. Thus, we attempt to prove whether Jun and Fos, a major member of the AP-1 family, are involved in the regulation of BORIS expression. Bioinformatics analysis revealed the existence of binding sites for Jun and Fos within the BORIS promoter. Through a series of overexpression and knockdown experiments, we corroborated that Jun and Fos have the capacity to augment BORIS expression, thereby fostering the migration and invasion of hepatocellular carcinoma cells. Moreover, Methylation-Specific PCR and Bisulfite Sequencing PCR assays revealed that Jun and Fos do not have a significant impact on the demethylation of the BORIS promoter. However, luciferase reporter and chromatin immunoprecipitation experiments substantiated that Jun and Fos could directly bind to the BORIS promoter, thereby enhancing its transcription. In conclusion, these results suggest that Jun and Fos can promote the development of hepatocellular carcinoma by directly regulating the expression of BORIS. These findings may provide experimental evidence positioning BORIS as a novel target for the clinical intervention of hepatocellular carcinoma.

Primary versus acquired epidermal growth factor receptor Thr790Met mutant non-small cell lung cancer: clinical features and prognoses.

PURPOSE: This study aimed to identify the impact of epidermal growth factor receptor (EGFR) T790M mutations on clinical characteristics and prognosis. METHODS: Retrospective analyses were conducted on the differences on clinicopathological features and prognosis between primary and acquired T790M mutations. Subgroup analyses were performed for primary T790M coexisting with other mutations. RESULTS: Patients with primary T790M mutations showed a 60.53% (23/38) incidence of concurrent L858R mutations, 18.42% (7/38) for 19del mutations and a 21.05% (8/38) occurrence of brain metastases. Conversely, those with acquired T790M mutations demonstrated respective frequencies of 36.53% (61/167), 58.68% (98/167) and 44.31% (74/167), with all comparisons yielding p < 0.05. The median overall survival differed significantly between the two groups, with a duration of 33 months for patients with primary T790M mutations as compared to 48 months for those with acquired mutations (p = 0.030). Notably, among patients with L858R co-mutations, when treated with third-generation EGFR-TKIs, those with acquired T790M mutations experienced a significantly prolonged median time to treatment failure compared to those with primary mutations (17 months vs. 9 months, p = 0.009). CONCLUSION: Patients with primary T790M have unique molecular features and had worse prognosis compared with acquired T790M. Resistance to third-generation EGFR-TKIs seems to be associated with the presence of EGFR co-mutations.

Impacts of climate warming and atmospheric deposition on recent shifts in chironomid communities in two alpine lakes, eastern China.

Climate warming and atmospheric deposition are altering alpine lake ecosystems at unprecedented rates, whereas their direct and indirect effects on primary consumer communities are unclear. This study presents sedimentary multi-proxy records including chironomids, diatoms, elements and stable isotopes of carbon and nitrogen in 210Pb-dated cores from two alpine lakes located above the timberline in the Taibai Mountain, eastern China. Before ∼2000 CE, chironomid communities were co-dominated by Heterotrissocladius marcidus-type and Micropsectra atrofasciata-type in the two lakes. Thereafter, Tanytarsus glabrescens-type increased rapidly to be a dominant species. Redundancy analyses (RDAs) revealed that chironomid fauna shifts were significantly correlated with rising diatom concentrations in both lakes, declining Ti content in the upstream lake and δ13C depletion in the downstream lake. Although temperature, precipitation and δ15N were not significant explanatory variables in RDAs, climate warming and atmospheric deposition likely promoted terrestrial and aquatic primary production, indicated by synchronous increases in organic matter contents and diatom concentrations in the two sediment cores. Since diatoms contain essential polyunsaturated fatty acids that are essential for chironomids, rising diatom concentrations can promote food quantity and quality. In addition, increased primary production would create organic substrates for chironomid larvae. Recent shifts in chironomid fauna driven by indirect effects of global warming and atmospheric deposition might be a widespread phenomenon in alpine lakes, probably triggering regime shifts in headwater lake ecosystems.

Features of Studies on Transition Interventions for Childhood Cancer Survivors: A Scoping Review.

PURPOSE: in this scoping review, previously reported data were described and synthesized to document transition interventions in CCSs, and the features of intervention components of the current transition studies for CCSs were summarized. METHODS: A literature search was conducted in PubMed, Web of Science, EMBASE, PsycINFO, CINAHL, Ovid, and the Cochrane Library following the PRISMA-ScR statement. All original studies (n = 9) investigating transition interventions in CCSs were included. RESULTS: The current studies identified essential elements for transition programs, such as delivering knowledge, developing skills for coordination of care, and addressing psychosocial needs. However, the current transition interventions were generally in their infancy, and major deficits were found, including poorly reported intervention components and procedures, a limited number of relevant validated outcomes, and a failure to incorporate conceptual frameworks and international consensus statements. CONCLUSIONS: This scoping review mapped current evidence of transition interventions for CCSs and highlighted the paucity of data in this area. More high-quality and well-reported randomized controlled trials are needed for the enrichment and standardization of future transition interventions.

Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status.

Introduction: Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

Introducción: Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC). Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricional se evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Los indicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, el grosor del pliegue cutáneo del tríceps y la circunferencia de las piernas. Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.481.222 ng/ml). Se observaron diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativas entre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales. La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml como umbral para EC. Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC.La leptina puede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.

T5S1607 identified as a antibacterial FtsZ inhibitor：Virtual screening combined with bioactivity evaluation for the drug discovery.

Due to antibiotic overuse, many bacteria have developed resistance, creating an urgent need for novel antimicrobial agents. It has been established that the filamentous temperature-sensitive mutant Z (FtsZ) of the bacterial cell division protein is an effective and promising antibacterial target. In this study, the optimal proteins were assessed by early recognition ability and the processed compound libraries were virtually screened using Vina. This effort resulted in the identification of 14 potentially active antimicrobial compounds. Among them, the compound T5S1607 demonstrated remarkable antibacterial efficacy against Bacillus subtilis ATCC9732 (MIC = 1 µg/mL) and Staphylococcus aureus ATC5C6538 (MIC = 4 µg/mL). Furthermore, in vitro experiments demonstrated that the selected compound T5S1607 rapidly killed bacteria and induced FtsZ protein aggregation, preventing bacterial division and leading to bacterial death. Additionally, cell toxicity and hemolysis experiments indicate that compound T5S1607 exhibits minimal toxicity to LO2 cells and shows no significant hemolytic effects on mammalian cells in vitro at the MIC concentration range. All the results indicate that compound T5S1607 is a promising antibacterial agent and a potential FtsZ inhibitor. In conclusion, this work successfully discovered FtsZ inhibitors with good activity through the virtual screening drug discovery process.