An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1.

Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains-a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase activity unexpectedly depends upon the holoenzyme protein TCAB1, which in turn controls conformation of CR4/5. Cells lacking TCAB1 exhibit a marked reduction in telomerase catalysis without affecting enzyme assembly. Instead, TCAB1 inactivation causes unfolding of CR4/5 helices that are required for catalysis and for association with the telomerase reverse-transcriptase (TERT). CR4/5 mutations derived from patients with telomere biology disorders provoke defects in catalysis and TERT binding similar to TCAB1 inactivation. These findings reveal a conformational "activity switch" in human telomerase RNA controlling catalysis and TERT engagement. The identification of two discrete catalytic states for telomerase suggests an intramolecular means for controlling telomerase in cancers and progenitor cells.

A LaCl3-based lithium superionic conductor compatible with lithium metal.

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

A long-duration gamma-ray burst with a peculiar origin.

It is generally believed that long-duration gamma-ray bursts (GRBs) are associated with massive star core collapse1, whereas short-duration GRBs are associated with mergers of compact star binaries2. However, growing observations3-6 have suggested that oddball GRBs do exist, and several criteria (prompt emission properties, supernova/kilonova associations and host galaxy properties) rather than burst duration only are needed to classify GRBs physically7. A previously reported long-duration burst, GRB 060614 (ref. 3), could be viewed as a short GRB with extended emission if it were observed at a larger distance8 and was associated with a kilonova-like feature9. As a result, it belongs to the type I (compact star merger) GRB category and is probably of binary neutron star (NS) merger origin. Here we report a peculiar long-duration burst, GRB 211211A, whose prompt emission properties in many aspects differ from all known type I GRBs, yet its multiband observations suggest a non-massive-star origin. In particular, substantial excess emission in both optical and near-infrared wavelengths has been discovered (see also ref. 10), which resembles kilonova emission, as observed in some type I GRBs. These observations point towards a new progenitor type of GRBs. A scenario invoking a white dwarf (WD)-NS merger with a post-merger magnetar engine provides a self-consistent interpretation for all the observations, including prompt gamma rays, early X-ray afterglow, as well as the engine-fed11,12 kilonova emission.

Wetland emission and atmospheric sink changes explain methane growth in 2020.

Atmospheric methane growth reached an exceptionally high rate of 15.1 ± 0.4 parts per billion per year in 2020 despite a probable decrease in anthropogenic methane emissions during COVID-19 lockdowns1. Here we quantify changes in methane sources and in its atmospheric sink in 2020 compared with 2019. We find that, globally, total anthropogenic emissions decreased by 1.2 ± 0.1 teragrams of methane per year (Tg CH4 yr-1), fire emissions decreased by 6.5 ± 0.1 Tg CH4 yr-1 and wetland emissions increased by 6.0 ± 2.3 Tg CH4 yr-1. Tropospheric OH concentration decreased by 1.6 ± 0.2 per cent relative to 2019, mainly as a result of lower anthropogenic nitrogen oxide (NOx) emissions and associated lower free tropospheric ozone during pandemic lockdowns2. From atmospheric inversions, we also infer that global net emissions increased by 6.9 ± 2.1 Tg CH4 yr-1 in 2020 relative to 2019, and global methane removal from reaction with OH decreased by 7.5 ± 0.8 Tg CH4 yr-1. Therefore, we attribute the methane growth rate anomaly in 2020 relative to 2019 to lower OH sink (53 ± 10 per cent) and higher natural emissions (47 ± 16 per cent), mostly from wetlands. In line with previous findings3,4, our results imply that wetland methane emissions are sensitive to a warmer and wetter climate and could act as a positive feedback mechanism in the future. Our study also suggests that nitrogen oxide emission trends need to be taken into account when implementing the global anthropogenic methane emissions reduction pledge5.

High-Throughput Single-Cell Sequencing with Linear Amplification.

Conventional methods for single-cell genome sequencing are limited with respect to uniformity and throughput. Here, we describe sci-L3, a single-cell sequencing method that combines combinatorial indexing (sci-) and linear (L) amplification. The sci-L3 method adopts a 3-level (3) indexing scheme that minimizes amplification biases while enabling exponential gains in throughput. We demonstrate the generalizability of sci-L3 with proof-of-concept demonstrations of single-cell whole-genome sequencing (sci-L3-WGS), targeted sequencing (sci-L3-target-seq), and a co-assay of the genome and transcriptome (sci-L3-RNA/DNA). We apply sci-L3-WGS to profile the genomes of >10,000 sperm and sperm precursors from F1 hybrid mice, mapping 86,786 crossovers and characterizing rare chromosome mis-segregation events in meiosis, including instances of whole-genome equational chromosome segregation. We anticipate that sci-L3 assays can be applied to fully characterize recombination landscapes, to couple CRISPR perturbations and measurements of genome stability, and to other goals requiring high-throughput, high-coverage single-cell sequencing.

The weekly cycle of photosynthesis in Europe reveals the negative impact of particulate pollution on ecosystem productivity.

Aerosols can affect photosynthesis through radiative perturbations such as scattering and absorbing solar radiation. This biophysical impact has been widely studied using field measurements, but the sign and magnitude at continental scales remain uncertain. Solar-induced fluorescence (SIF), emitted by chlorophyll, strongly correlates with photosynthesis. With recent advancements in Earth observation satellites, we leverage SIF observations from the Tropospheric Monitoring Instrument (TROPOMI) with unprecedented spatial resolution and near-daily global coverage, to investigate the impact of aerosols on photosynthesis. Our analysis reveals that on weekends when there is more plant-available sunlight due to less particulate pollution, 64% of regions across Europe show increased SIF, indicating more photosynthesis. Moreover, we find a widespread negative relationship between SIF and aerosol loading across Europe. This suggests the possible reduction in photosynthesis as aerosol levels increase, particularly in ecosystems limited by light availability. By considering two plausible scenarios of improved air quality-reducing aerosol levels to the weekly minimum 3-d values and levels observed during the COVID-19 period-we estimate a potential of 41 to 50 Mt net additional annual CO2 uptake by terrestrial ecosystems in Europe. This work assesses human impacts on photosynthesis via aerosol pollution at continental scales using satellite observations. Our results highlight i) the use of spatiotemporal variations in satellite SIF to estimate the human impacts on photosynthesis and ii) the potential of reducing particulate pollution to enhance ecosystem productivity.

Microfluidics-Derived Microparticles with Prebiotics and Probiotics for Enhanced In Situ Colonization and Immunoregulation of Colitis.

Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.

Dimensional and Doping Engineering of Chiral Perovskites with Enhanced Spin Selectivity for Green Emissive Spin Light-Emitting Diodes.

Chiral perovskites play a pivotal role in spintronics and optoelectronic systems attributed to their chiral-induced spin selectivity (CISS) effect. Specifically, they allow for spin-polarized charge transport in spin light-emitting diodes (LEDs), yielding circularly polarized electroluminescence at room temperature without external magnetic fields. However, chiral lead bromide-based perovskites have yet to achieve high-performance green emissive spin-LEDs, owing to limited CISS effects and charge transport. Herein, we employ dimensional regulation and Sn2+-doping to optimize chiral bromide-based perovskite architecture for green emissive spin-LEDs. The optimized (PEA)x(S/R-PRDA)2-xSn0.1Pb0.9Br4 chiral perovskite film exhibits an enhanced CISS effect, higher hole mobility, and better energy level alignment with the emissive layer. These improvements allow us to fabricate green emissive spin-LEDs with an external quantum efficiency (EQE) of 5.7% and an asymmetry factor |gCP-EL| of 1.1 × 10-3. This work highlights the importance of tailored perovskite architectures and doping strategies in advancing spintronics for optoelectronic applications.

K33 only mutant ubiquitin augments bone marrow-derived dendritic cell-mediated CTL priming via PI3K-Akt pathway.

To explore the effect of K33 only mutant ubiquitin (K33O) on bone marrow-derived dendritic cells' (BMDCs') maturity, antigen uptake capability, surface molecule expressions and BMDC-mediated CTL priming, and further investigate the role of PI3K-Akt engaged in K33O-increased BMDC maturation, antigen uptake and presentation, surface molecule expressions and BMDC-based CTL priming. BMDCs were conferred K33O and other ubiquitin mutants (K33R, K48R, K63R-mutant ubiquitin) incubation or LY294002 and wortmannin pretreatment. PI3K-Akt phosphorylation, antigen uptake, antigenic presentation and CD86/MHC class I expression in BMDC were determined by western blot or flow cytometry. BMDC-based CTL proliferation and priming were determined by in vitro mixed lymphocyte reaction (MLR), ex vivo enzyme-linked immunospot assay (Elispot) and flow cytometry with intracellular staining, respectively. The treatment with K33O effectively augmented PI3K-Akt phosphorylation, BMDCs' antigen uptake, antigenic presentation, CD86/MHC class I and CD11c expressions. MLR, Elispot and flow cytometry revealed that K33O treatment obviously enhanced CTL proliferation, CTL priming and perforin/granzyme B expression. The pretreatment with PI3K-Akt inhibitors efficiently abrogated K33O's effects on BMDC. The replenishment of K33 only mutant ubiquitin augments BMDC-mediated CTL priming in bone marrow-derived dendritic cells via PI3K-Akt signalling.

Phase I trial of apatinib and paclitaxel+oxaliplatin+5-FU/levoleucovorin for treatment-naïve advanced gastric cancer.

Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment-naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional "3 + 3" study design. Among 21 treated patients, one experienced a dose-limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3-4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand-foot syndrome (14.3%). Median progression-free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first-line treatment for AGC in a larger study.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer.

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)2Sr2CuO6+δ.

The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.

Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Beyond the visible: Accounting for ultraviolet and far-red radiation in vegetation productivity and surface energy budgets.

Photosynthetically active radiation (PAR) is typically defined as light with a wavelength within 400-700 nm. However, ultra-violet (UV) radiation within 280-400 nm and far-red (FR) radiation within 700-750 nm can also excite photosystems, though not as efficiently as PAR. Vegetation and land surface models (LSMs) typically do not explicitly account for UV's contribution to energy budgets or photosynthesis, nor FR's contribution to photosynthesis. However, whether neglecting UV and FR has significant impacts remains unknown. We explored how canopy radiative transfer (RT) and photosynthesis are impacted when explicitly implementing UV in the canopy RT model and accounting for UV and FR in the photosynthesis models within a next-generation LSM that can simulate hyperspectral canopy RT. We validated our improvements using photosynthesis measurements from plants under different light sources and intensities and surface reflection from an eddy-covariance tower. Our model simulations suggested that at the whole plant level, after accounting for UV and FR explicitly, chlorophyll content, leaf area index (LAI), clumping index, and solar radiation all impact the modeling of gross primary productivity (GPP). At the global scale, mean annual GPP within a grid would increase by up to 7.3% and the increase is proportional to LAI; globally integrated GPP increases by 4.6 PgC year-1 (3.8% of the GPP without accounting for UV + FR). Further, using PAR to proxy UV could overestimate surface albedo by more than 0.1, particularly in the boreal forests. Our results highlight the importance of improving UV and FR in canopy RT and photosynthesis modeling and the necessity to implement hyperspectral or multispectral canopy RT schemes in future vegetation and LSMs.

Differential pressure sensors based on transfer-free piezoresistive layered PdSe2thin films.

Piezoresistive layered two-dimensional (2D) crystals offer intriguing promise as pressure sensors for microelectromechanical systems (MEMS) due to their remarkable strain-induced conductivity modulation. However, integration of the conventional chemical vapor deposition grown 2D thin films onto a micromachined silicon platform requires a complex transfer process, which degrades their strain-sensing performance. In this study, we present a differential pressure sensor built on a transfer-free piezoresistive PdSe2polycrystalline film deposited on a SiNxmembrane by plasma-enhanced selenization of a metal film at a temperature as low as 200 °C. Based on the resistance change and finite element strain analysis of the film under membrane deflection, we show that a 7.9 nm thick PdSe2film has a gauge factor (GF) of -43.3, which is ten times larger than that of polycrystalline silicon. The large GF enables the development of a diaphragm pressure sensor with a high sensitivity of 3.9 × 10-4kPa-1within the differential pressure range of 0-60 kPa. In addition, the sensor with a Wheatstone bridge circuit achieves a high voltage sensitivity of 1.04 mV·kPa-1, a rapid response time of less than 97 ms, and small output voltage variation of 8.1 mV in the temperature range of 25 °C to 55 °C. This transfer-free and low-temperature grown PdSe2piezoresistive thin film is promising for MEMS transducer devices.

Assessing the impact of early progressive mobilization on moderate-to-severe traumatic brain injury: a randomized controlled trial.

INTRODUCTION: Traumatic brain injury (TBI) is a major cause of neurodisability worldwide, with notably high disability rates among moderately severe TBI cases. Extensive previous research emphasizes the critical need for early initiation of rehabilitation interventions for these cases. However, the optimal timing and methodology of early mobilization in TBI remain to be conclusively determined. Therefore, we explored the impact of early progressive mobilization (EPM) protocols on the functional outcomes of ICU-admitted patients with moderate to severe TBI. METHODS: This randomized controlled trial was conducted at a trauma ICU of a medical center; 65 patients were randomly assigned to either the EPM group or the early progressive upright positioning (EPUP) group. The EPM group received early out-of-bed mobilization therapy within seven days after injury, while the EPUP group underwent early in-bed upright position rehabilitation. The primary outcome was the Perme ICU Mobility Score and secondary outcomes included Functional Independence Measure motor domain (FIM-motor) score, phase angle (PhA), skeletal muscle index (SMI), the length of stay in the intensive care unit (ICU), and duration of ventilation. RESULTS: Among 65 randomized patients, 33 were assigned to EPM and 32 to EPUP group. The EPM group significantly outperformed the EPUP group in the Perme ICU Mobility and FIM-motor scores, with a notably shorter ICU stay by 5.9 days (p < 0.001) and ventilation duration by 6.7 days (p = 0.001). However, no significant differences were observed in PhAs. CONCLUSION: The early progressive out-of-bed mobilization protocol can enhance mobility and functional outcomes and shorten ICU stay and ventilation duration of patients with moderate-to-severe TBI. Our study's results support further investigation of EPM through larger, randomized clinical trials. Clinical trial registration ClinicalTrials.gov NCT04810273 . Registered 13 March 2021.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study.

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. RESULTS: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]). CONCLUSION: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Sex-specific grey matter abnormalities in individuals with chronic insomnia.

Previous studies have reported sex differences in altered brain function in patients with chronic insomnia (CI). However, sex-related alterations in brain morphology have rarely been investigated. This study aimed to investigate sex-specific grey matter (GM) alterations in patients with CI and to examine the relationship between GM alterations and neuropsychological assessments. Ninety-three (65 females and 28 males) patients and 78 healthy (50 females and 28 males) controls were recruited. Structural magnetic resonance imaging data were analysed using voxel-based morphometry to test for interactions between sex and diagnosis. Spearman's correlation was used to assess the associations among structure, disease duration, and sleep-, mood-, and cognition-related assessments. Males with CI showed reduced GM volume in the left inferior parietal lobe, left middle cingulate cortex, and right supramarginal gyrus. Females with CI showed increased GM volume in the right Rolandic operculum. Moreover, mood-related assessments were negatively correlated with GM volumes in the right supramarginal gyrus and left inferior parietal lobe in the male patients, and cognitive-related assessments were positively correlated with GM volumes in the Rolandic operculum in the female patients. Our findings indicate sex-specific alterations in brain morphology in CI, thereby broadening our understanding of sex differences in CI and potentially providing complementary evidence for the development of more effective therapies and individual treatments.