Physiological and psychological recovery in two pure forests: interaction between perception methods and perception durations.

The forest experience is good for people's physical and mental health. However, few studies on the effects of pure forest based on the duration and way of experience on people's physical and mental recovery. In this study, we took 180 first-year college students as research objects and conducted experiments in Pinus sylvestris and Betula platyphylla and the control group of grass plot. The changes of physiological and psychological indexes of the subjects were compared by two perception methods (onsite perception, video perception) and three perception duration (10 min, 20 min, 30 min). The results indicated that: (1) Differences between the two pure forests were mainly reflected in short-term recovery of diastolic blood pressure (DBP) and long-term recovery of total mood disorder (TMD). (2) Video perception was more conducive to short-term recovery of systolic blood pressure (SBP) and diastolic blood pressure (DBP). (3) Viewing the Pinus sylvestris for 20 min in different ways was the best way to relieve stress. It is suggested that, Pinus sylvestris can be used as the rehabilitation perception material, and reasonable path length or perception time can be selected for landscape construction in future. These results can provide scientific reference for landscape design based on forest health and environmental perception.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Psychometric validation of the PERMA-profiler for well-being in Chinese adults.

Well-being is one of the central topics in psychology, and research on this topic has shifted from emotional experiences to flourishing life in recent years. Seligman's PERMA model is a prominent theory in this shift. However, this model is proposed in Western culture and has yet to be empirically validated in the Chinese context. The present research aims to examine the applicability of the five-dimension PERMA-Profiler in Chinese culture, which has been developed based on the PERMA model. A sample of 1468 Chinese adults participated in the research. After translation and validation, a series of psychometric analyses were conducted to examine the internal consistency reliability, construct validity, convergent and discriminant validity, and factorial invariance across genders. The PERMA-Profiler Chinese showed high Cronbach's alpha coefficients (α = 0.79-0.88), good divergent (r = -0.19 to -0.38) and convergent validity (r = 0.53-0.85), as well as satisfactory structural validity. Results of the structural validity demonstrated a better fit to the first-order model with five correlated factors after modification (χ2/df = 4.65, RMSEA = 0.058, SRMR = 0.030, CFI = 0.943, TLI = 0.924) than the second-order model with a higher-order factor of well-being. However, the engagement dimension of the PERMA-Profiler Chinese could be improved further. In conclusion, the PERMA model is applicable to the Chinese culture, and the PERMA-Profiler provides a valid measure of well-being for Chinese adults.

Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

Organic-inorganic hybrid material for hole transport in inverted perovskite solar cells.

Hole mobility is critical to the power conversion efficiencies of perovskite solar cells (PSCs). Organic small-molecule hole-transporting materials (HTMs) have attracted considerable interest in PSCs due to their structural flexibility and operational durability, but they suffer from modest hole mobility. On the other hand, inorganic HTMs with good hole mobility are inflexible in structural variation and exhibit unsatisfactory cell efficiency. In this study, a ligand BT28 and its zinc-based coordination complex BTZ30 were synthesized, characterized, and investigated as HTMs for PSC applications. The mixed-halide perovskites can be grown uniformly with large crystalline grains on both HTMs, which exhibit similar optical and electrochemical properties. However, it was discovered that the BTZ30-based solar cell exhibited an open-circuit voltage of 1.0817 V and a high short-circuit current density of 23.1392 mA cm-2 with a champion power conversion efficiency of close to 20 %. The performance difference between the two HTMs can be attributed to the difference in their hole mobilities, which is 63.31 % higher for BTZ30 than BT28. The comparison of non-metal and metal HTMs revealed the importance of considering hybrid structures to overcome some shortcomings associated with organic and inorganic HTMs and achieve high-performance PSCs.

[Effects of denosumab on bone mineral density around proximal femoral prosthesis after total hip replacement in postmenopausal osteoporotic patients].

OBJECTIVE: To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients. METHODS: Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured. RESULTS: At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation. CONCLUSION: After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.

The second docetaxel rechallenge for metastatic castration-resistant prostate cancer: a case report.

Background: Docetaxel combined with prednisone plus androgen deprivation therapy (ADT) is the preferred treatment option for metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC). With the development of next-generation hormonal agents (NHAs) and poly (ADP-ribose) polymerase (PARP) inhibitors, more aggressive first-line or later-line treatment strategies have been added to the treatment of mHSPC and mCRPC. However, docetaxel rechallenge (DR) has special clinical significance in patients with "docetaxel-sensitive" prostate cancer. There are no reports on the efficacy and safety of the second DR in mCRPC patients. Case presentation: We report one patient diagnosed with mCRPC who showed progression-free survival (PFS) and overall survival (OS) benefits and safety and good lower urinary tract function after the second DR. Conclusion: The second DR as a potential alternative later-line treatment strategy should be considered for patients with mCRPC who worry about the high economic burden of multigene molecular testing and PARP inhibitors as well as repeated prostate needle biopsy.

An ultrasensitive J-shaped optical fiber LSPR aptasensor for the detection of Helicobacter pylori.

The development of label-free and sensitive detection of pathogenic bacteria is of great significance for disease prevention and public health protection. In this study, an originally bent structure, named as J-shaped optical fiber probe, was first designed to engineer a localized surface plasmon resonance (LSPR) aptamer biosensor for the rapid and ultrasensitive detection of Helicobacter pylori (H. pylori). The J-shaped optical fiber probe exhibited a significant improvement in refractive index sensitivity (RIS) and LSPR signal response. Meantime, the original sequence of aptamer was truncated in order to effectively capture H. pylori on the optical fiber surface. Besides, a spacer nucleic acid with short stem-loop structure was adopted to control the aptamer density on gold nanoparticles (AuNPs) on the surface of the J-shaped optical fiber probe, which displayed a further enhancement in LSPR signal response. Benefitting from these creative designs, the proposed LSPR biosensor can realize label-free and sensitive detection of H. pylori with a detection limit as low as 45 CFU/mL and a wide linear range from 1.0 × 102 CFU/mL to 1.0 × 108 CFU/mL. At the same time, the sensing strategy can detect the pathogenic bacteria from actual water samples in one step just in 30 min without any sample pretreatment. Due to the advantages of ease-to-preparation, high sensitivity, and rapid analysis, this proposed J-shaped optical fiber LSPR aptasensor can provide a potential strategy for point-of-caring detection of pathogenic bacteria in environmental monitoring and disease diagnosis.

The adaptation of root cell wall pectin to copper toxicity in two citrus species differing in copper tolerance: remodeling and responding.

Citrus species are prone to suffer from copper (Cu) toxicity because of improper application of Cu-based agrochemicals. Copper immobilization mediated by pectin methylesterase (PME) in the root cell wall (CW) is effective for Cu detoxification. However, the underlying mechanisms of the structural modification and stress responses of citrus root CW pectin to Cu toxicity have been less discussed. In the present study, seedlings of 'Shatian pummelo' (Citrus grandis L. Osbeck) and 'Xuegan' (Citrus sinensis L. Osbeck), which differ in Cu tolerance, were irrigated with nutrient solution containing 0.5 (as control), 100, 300 or 500 µM Cu for 18 weeks in sandy culture or 24 h in hydroponics. At the end of treatments in the 18-week sandy culture, Cu toxicity on CW pectin content, Cu distribution, degree of pectin methylesterification (DPM) and the PME enzyme activity were discussed. At the genome-wide level, PME gene family was identified from the two citrus species, and qRT-PCR array of citrus PMEs under control and 300 µM Cu stress for 18 weeks were performed to screen the Cu-responsive PME genes. Moreover, the candidate genes that responded to Cu toxicity were further examined within 24 h. The results showed that Cu toxicity increased the root CW pectin content. The root CW pectin under Cu toxicity was remodeled by upregulation of the expression of the Cu-responsive PME genes followed by increasing PME activity, which mainly promoted low methylesterased pectin level and the Cu content on root CW pectin. Compared with C. sinensis, C. grandis root CW had a lower DPM and higher Cu content on the Cu-stressed root CW pectin, contributing to its higher Cu tolerance. Our present study provided theoretical evidence for root CW pectin remodeling in response to Cu toxicity of citrus species.

Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

Copy number alteration features in pan-cancer homologous recombination deficiency prediction and biology.

Homologous recombination deficiency (HRD) renders cancer cells vulnerable to unrepaired double-strand breaks and is an important therapeutic target as exemplified by the clinical efficacy of poly ADP-ribose polymerase (PARP) inhibitors as well as the platinum chemotherapy drugs applied to HRD patients. However, it remains a challenge to predict HRD status precisely and economically. Copy number alteration (CNA), as a pervasive trait of human cancers, can be extracted from a variety of data sources, including whole genome sequencing (WGS), SNP array, and panel sequencing, and thus can be easily applied clinically. Here we systematically evaluate the predictive performance of various CNA features and signatures in HRD prediction and build a gradient boosting machine model (HRDCNA) for pan-cancer HRD prediction based on these CNA features. CNA features BP10MB[1] (The number of breakpoints per 10MB of DNA is 1) and SS[ > 7 & <=8] (The log10-based size of segments is greater than 7 and less than or equal to 8) are identified as the most important features in HRD prediction. HRDCNA suggests the biallelic inactivation of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BARD1 as the major genetic basis for human HRD, and may also be applied to effectively validate the pathogenicity of BRCA1/2 variants of uncertain significance (VUS). Together, this study provides a robust tool for cost-effective HRD prediction and also demonstrates the applicability of CNA features and signatures in cancer precision medicine.

Effects of brief exposure to campus environment on students' physiological and psychological health.

Experiences in natural environments can enhance human wellbeing and promote the recovery of physiological and psychological health. During the COVID-19 pandemic, university students' activity off-campus was limited, thus, the campus environment was particularly important for the recovery of students' physiological and psychological health. Although the benefits of sustained natural exposure are obvious for people's physiological and psychological health, the effects of brief exposure on physiological and psychological are unclear. In the present study, four types of campus environments, including square space, dense forest space, sparse forest space, and waterfront space, were selected to explore the transient recovery effects of different types of campus environments. Sixty university students were recruited, measuring their systolic blood pressure, diastolic blood pressure, and heart rate as physical parameters to assess stress recovery. Respondents also reported scores about their personal feelings in questionnaires to evaluate their psychological states. Both physiological and psychological indicators responded to the brief natural exposure (5 min), and physiological and psychological health was restored. However, only the recovery amounts of psychological indicators were significantly different in waterfront space, dense forest space, and sparse forest space. These results indicate that being compare with other spaces, the brief exposure in the waterfront space was the most beneficial to students' psychological health recovery. This recovery was attributed to the great role played by the sense of escape, but after the brief exposure, the attraction and compatibility of the environment would hinder the psychological health recovery. In conclusion, according to tests on both physiological and psychological aspects, the waterfront environment on campus is the best choice for students' transient health recovery.

Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Accurate prediction of pan-cancer types using machine learning with minimal number of DNA methylation sites.

DNA methylation analysis has been applied to determine the primary site of cancer; however, robust and accurate prediction of cancer types with a minimum number of sites is still a significant scientific challenge. To build an accurate and robust cancer type prediction tool with a minimum number of DNA methylation sites, we internally benchmarked different DNA methylation site selection and ranking procedures, as well as different classification models. We used The Cancer Genome Atlas dataset (26 cancer types with 8296 samples) to train and test models and used an independent dataset (17 cancer types with 2738 samples) for model validation. A deep neural network model using a combined feature selection procedure (named MethyDeep) can predict 26 cancer types using 30 methylation sites with superior performance compared with the known methods for both primary and metastatic cancers in independent validation datasets. In conclusion, MethyDeep is an accurate and robust cancer type predictor with the minimum number of DNA methylation sites; it could help the cost-effective clarification of cancer of unknown primary patients and the liquid biopsy-based early screening of cancers.

Ω-shaped fiber optic LSPR biosensor based on mismatched hybridization chain reaction and gold nanoparticles for detection of circulating cell-free DNA.

Circulating cell-free DNA (cfDNA) is a promising biomarker of liquid biopsy, but it still faces some difficulties in achieving sensitive and convenient detection. Herein, an Ω-shaped fiber optic localized surface plasmon resonance (FO-LSPR) biosensor based on hybridization chain reaction (HCR) coupled with gold nanoparticles (AuNPs) was developed, and applied in simple and sensitive detection of cfDNA. Specifically, one-base mismatch was designed in HCR hairpins (H1 and H2) to obtain high reaction efficiency, and AuNPs was introduced onto H1 through poly-adenine to construct HCR coupled with AuNPs strategy. Meanwhile, target cfDNA was designed into two domains: one could trigger HCR to generate dsDNA concatemer carrying numerous AuNPs, and the other could hybridize with capture DNA on the surface of Ω-shaped fiber optic (FO) probes. Thus, the presence of target cfDNA would initiate HCR, and bring the formed dsDNA concatemer and AuNPs to approach the probe surface, resulting in dramatically amplified LSPR signal. Besides, HCR required simple isothermal and enzyme-free condition, and Ω-shaped FO probe with high refractive index sensitivity just needed to be immersed into HCR solution directly for signal monitoring. Benefiting from the synergetic amplification of mismatched HCR and AuNPs, the proposed biosensor exhibited high sensitivity with a limit of detection of 14.0 pM, and therefore could provide a potential strategy for biomedical analysis and disease diagnosis.

Trends in Swallowing Outcomes Following Deintensified Treatment in Selected p16+ Oropharyngeal Carcinoma.

Objective: Identify trends in swallowing outcomes in p16+ oropharyngeal squamous cell carcinoma following neoadjuvant chemotherapy+surgery (NAC+S) versus neoadjuvant chemotherapy+surgery+radiation (NAC+S+R). Study Design: Cohort study. Setting: Single academic institution. Methods: Swallowing outcome was measured using a validated questionnaire, MD Anderson Dysphagia Inventory (MDADI). MDADI scores were compared between NAC+S and NAC+S+R groups in short-term (<1 year), middle-term (1-3 years), and long-term (>3 years). Clinical factors associated with MDADI scores were explored using a linear mixed model. Statistical significance was established at p < .05. Results: Sixty-seven patients met the inclusion criteria and were divided into 2 groups: NAC+S (57 [85.1%]) and NAC+S+R (10 [14.9%]). All patients had improved MDADI scores in the middle-term compared to short-term (NAC+S: score increase = 3.43, p = .002; NAC+S+R: score increase = 11.18, p = .044), long-term compared to short-term (NAC+S: score increase = 6.97, p < .001; NAC+S+R: score increase = 20.35, p < .001), and long-term compared to middle-term (NAC+S: score increase = 3.54, p = .043; NAC+S+R: score increase = 9.18, p = .026). NAC+S patients had better MDADI scores than NAC+S+R patients at short-term (83.80 vs 71.26, p = .001). There was no significant difference in swallowing function in the middle-term or long-term. Conclusion: Regardless of treatment type, swallowing will likely be improved in the middle-term and long-term compared to the short-term. Patients treated with NAC+S+R will have worse short-term swallowing function. However, in the middle-term and long-term, there is no significant difference in swallowing function between patients treated with NAC+S and NAC+S+R.

Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit. CASE PRESENTATION: We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction. CONCLUSION: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

TLimmuno2: predicting MHC class II antigen immunogenicity through transfer learning.

Major histocompatibility complex (MHC) class II molecules play a pivotal role in antigen presentation and CD4+ T cell response. Accurate prediction of the immunogenicity of MHC class II-associated antigens is critical for vaccine design and cancer immunotherapies. However, current computational methods are limited by insufficient training data and algorithmic constraints, and the rules that govern which peptides are truly recognized by existing T cell receptors remain poorly understood. Here, we build a transfer learning-based, long short-term memory model named 'TLimmuno2' to predict whether epitope-MHC class II complex can elicit T cell response. Through leveraging binding affinity data, TLimmuno2 shows superior performance compared with existing models on independent validation datasets. TLimmuno2 can find real immunogenic neoantigen in real-world cancer immunotherapy data. The identification of significant MHC class II neoantigen-mediated immunoediting signal in the cancer genome atlas pan-cancer dataset further suggests the robustness of TLimmuno2 in identifying really immunogenic neoantigens that are undergoing negative selection during cancer evolution. Overall, TLimmuno2 is a powerful tool for the immunogenicity prediction of MHC class II presented epitopes and could promote the development of personalized immunotherapies.

Bazedoxifene attenuates intestinal injury in sepsis by suppressing the NF-κB/NLRP3 signaling pathways.

Acute inflammatory injury is the primary cause of sepsis, leading to various organ failures. Bazedoxifene (BAZ) has been proven to have anti-inflammatory effects. However, its effects on sepsis-induced intestinal injury are unclear. Here, we demonstrated the beneficial effects of BAZ on intestinal injury and explored the underlying mechanisms using cecal ligation and perforation (CLP)-mediated sepsis mouse model and in vitro cultured intestinal epithelial MODE-K cells. We found that BAZ elevated the survival rate of septic mice and attenuated CLP-triggered intestinal damage. BAZ inhibited intestinal inflammation and restored the impaired intestinal barriers in CLP mice. The mechanistic study in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated MODE-K cells showed that BAZ significantly downregulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), caspase-1, and gasdermin D (GSDMD), and markedly reduced the phosphorylation of molecules in the nuclear factor kappa B (NF-κB) pathway. Moreover, BAZ prominently rescued the decreased viability of MODE-K cells and reduced lactate dehydrogenase (LDH) release upon LPS/ATP challenge. However, BAZ did not affect the inflammasome assembly, as evidenced by the lack of changes in ASC (apoptosis speck-like protein containing a CARD) speck formation. Our results suggest that BAZ relieves inflammation and intestinal barrier function disruption by suppressing the NF-κB/NLRP3 signaling pathways. Therefore, BAZ is a potential therapeutic candidate for treating intestinal injury in sepsis.

Superconductivity in single-crystalline ZrTe3-x (x ≤ 0.5) nanoplates.

Superconductivity with an unusual filamented character below 2 K has been reported in bulk ZrTe3 crystals, a well-known charge density wave (CDW) material, but still lacks in its nanostructures. Here, we systemically investigated the transport properties of controllable chemical vapor transport synthesized ZrTe3-x nanoplates. Intriguingly, superconducting behavior is found at T c = 3.4 K and can be understood by the suppression of CDW due to the atomic disorder formed by Te vacancies. Magnetic field and angle dependent upper critical field revealed that the superconductivity in the nanoplates exhibits a large anisotropy and two-dimensional character. This two-dimensional nature of superconductivity was further satisfactorily described using the Berezinsky-Kosterlitz-Thouless transition. Our results not only demonstrate the critical role of Te vacancies for superconductivity in ZrTe3-x nanoplates, but also provide a promising platform to explore the exotic physics in the nanostructure devices.