Approaches for Lynch syndrome screening and characteristics of subtypes with mismatch repair deficiency in patients with colorectal carcinoma.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening.

Designing Dense, Robust, and Ion-Diffusion-Effective Electrodes from Natural Wood Material toward High-Volumetric-Performance Supercapacitors.

Assembling active materials into dense electrodes is a promising way to obtain high-volumetric-capacitance supercapacitors, but insufficient ion channels in the dense structure lead to a low rate capability. Herein, a dense and robust wood electrode with a large MXene volumetric mass loading (1.25 g cm-3) and abundant ion diffusion channels is designed via a facile capillary-force-driven self-densification strategy. Specifically, MXene is assembled onto a wood cell wall, endowing the wood electrode with good electrical conductivity (86 S cm-1) and high electrochemical activity (5.9 F cm-2 at 1 mA cm-2). Notably, the oriented channels along with spaces between adjacent microfibrils recast after densification ensure efficient ion transport for the wood electrode, achieving an excellent rate capability with a high capacitance retention of 77% from 1 to 20 mA cm-2. Meanwhile, the capillary force induces self-densification on the softened wood cell wall, resulting in a highly compact and robust structure for the wood electrode.

Expanding the Spectrum of NUTM1 -Rearranged Sarcoma : A Clinicopathologic and Molecular Genetic Study of 8 Cases.

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1 -rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1 -rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.

The development and implementation of pathological parameters and molecular testing impact prognosis of colorectal adenocarcinoma.

Objective: This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer (CRC) patients in Fudan University Shanghai Cancer Center (FUSCC). Methods: This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020. Patients were divided into five groups for different analytical purposes: (1) the before vs. since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients; (2) the partial vs. total mesorectal excision (TME) groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients; (3) the tumor deposit (TD)(+)N0 vs. TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis (LNM); (4) the before vs. since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients; and (5) the groups with vs. without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients. Patients' clinicopathological parameters, including age at diagnosis, sex, tumor size, location, differentiation, mucinous subtype, TD, lymphovascular invasion, perineural invasion, tumor depth, LNM and distant metastasis, and tumor-node-metastasis (TNM) stage, were compared between groups. Kaplan-Meier analysis with log rank method was performed for patients' overall survival (OS) and disease-free survival (DFS) analyses. Results: In pathological reports, there were three parameter changes that impacted patient outcomes. Firstly, changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1: 110.9 to 1: 0.26. In comparison to patients admitted before 2014 (n = 4,754), a significant difference in prognosis between pT3 and pT4 stages was observed since 2014 (n = 9,965). Secondly, we began to evaluate the completeness of the mesorectum since 2016. As a result, 91.0% of patients with low rectal cancer underwent TME (n = 4,111) surgery, and patients with TME had significantly better OS compared with partial mesorectal excision (PME, n = 409). Thirdly, we began to stage TD (+) LNM (-) as N1c since 2017. The results showed that N1c (n = 127) but not N0 (n = 39) can improve the prognosis of patients without LNM and distal metastasis. In molecular testing, there have been three and five iterations of updates regarding mismatch repair (MMR)/microsatellite instability (MSI) status and RAS/BRAF gene mutation detection, respectively. The standardization of MMR status testing has sharply decreased the proportion of deficient MMR (dMMR) patients (from 32.5% to 7.4%) since 2013. The prognosis of patients underwent MMR status testing since 2013 (n = 867) were significantly better than patients before 2013 (n = 1,313). In addition, detection of RAS/BRAF gene mutation status (n = 5,041) resulted in better DFS but not OS, for patients with stage I-III disease (n = 16,557). Conclusion: Over the past few decades, updates in elements in pathological reports, as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.

Clinical application of FIGO 2023 staging system of endometrial cancer in a Chinese cohort.

OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer (EC) was released with incorporating histology, lympho-vascular space invasion, and molecular classification together. Our objective is to further explore the clinical utility and prognostic significance of the 2023 FIGO staging system in China. METHODS: A retrospective analysis was conducted for patients who received standard surgeries and underwent genetic testing using multigene next-generation sequencing (NGS) panels between December 2018 and December 2023 at Fudan University Shanghai Cancer Center, Shanghai, China. The genomic and clinical data of all patients were analyzed, and stages were determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 547 patients were enrolled in the study. After the restaged by the FIGO 2023 staging system, stage shifts occurred in 147/547 (26.9%) patients. In patients with early stages in FIGO 2009 (stage I-II), 63 cases were rearranged to IAmPOLEmut and 53 cases to IICmp53abn due to the molecular classification of POLEmut and p53abn. Altogether 345 cases were in stage I, 107 cases in stage II, 69 cases in stage III, and 26 cases in stage IV according to the FIGO 2023 staging criteria. For stage I diseases, the 3-year PFS rate was 92.7% and 95.3% in 2009 and 2023 FIGO staging systems, respectively. The 3-year PFS of stage II in 2023 FIGO was lower than that of FIGO 2009 (3-year PFS: 85.0% versus 90.9%), especially in substage IIC and IICmp53abn. Three cases (12%) of stage IIIA in FIGO 2009 were shifted to stage IA3 FIGO 2023, with 3-year PFS rates of 90.9% versus 100%, respectively. In NGS analysis, the most prevalent gene alterations were observed in PTEN and PIK3CA. CONCLUSION: The FIGO 2023 staging system was proved to be a good predictor of survival for EC patients with enhanced precision compared to FIGO 2009. Predominant stage shifts were observed in early-stage diseases. Distinct gene alterations of different subtypes may help to explore more accurate target therapies.

Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

BACKGROUND: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. METHODS: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). FINDINGS: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. INTERPRETATION: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. FUNDING: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Cooperative amplification of Prussian blue as a signal indicator and functionalized metal-organic framework-based electrochemical biosensor for an ultrasensitive HE4 assay.

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.

Effects of functional defects in the NMD pathway on rice phenotype and transcriptome.

Nonsense-mediated mRNA decay (NMD) is an important RNA quality control pathway. It aids in degrading harmful erroneous mRNA, thereby preserving a stable and healthy internal environment. In this study, we employed CRISPR/Cas9 and amiRNA technology to generate knock out or knock down mutants of realted genes in the rice NMD pathway. Through transcriptome sequencing and observing phenotype changes, the study explored the impact of NMD pathway defects on rice gene expression and alternative splicing. The results suggest that even partial defects will induce phenotypic changes such as plant height and pollen vitality to different degrees, showing necessity of NMD factors. Gene expression analysis reveals that most differentially expressed genes are upregulated in the mutants, with ko-upf1-like and kd-upf1 defects having a more significant impact than kd-upf2 and kd-upf3. Specifically, NMD pathway defects result in increased expression levels of rice defense response-related genes and decreased expression levels of secondary metabolism-related genes, with a wider range of affected genes observed in 60-day-old senescence mutants. Transcript analysis indicates that different NMD related genes defects alter hundreds of alternative splicing events, mostly enriched in genes involving alternative splicing regulatory pathways. Approximately half of these events are shared among different mutants, and a substantial number of affected transcripts show NMD target features. NMD could affect both the transcript abundance and their splicing subtypes to regulate the defense response and early-senescence associated pathways, which plays a vital role in rice growth and reproduction.

Organic Thermoelectric Materials for Wearable Electronic Devices.

Wearable electronic devices have emerged as a pivotal technology in healthcare and artificial intelligence robots. Among the materials that are employed in wearable electronic devices, organic thermoelectric materials possess great application potential due to their advantages such as flexibility, easy processing ability, no working noise, being self-powered, applicable in a wide range of scenarios, etc. However, compared with classic conductive materials and inorganic thermoelectric materials, the research on organic thermoelectric materials is still insufficient. In order to improve our understanding of the potential of organic thermoelectric materials in wearable electronic devices, this paper reviews the types of organic thermoelectric materials and composites, their assembly strategies, and their potential applications in wearable electronic devices. This review aims to guide new researchers and offer strategic insights into wearable electronic device development.

Novel Pan-Coronavirus 3CL Protease Inhibitor MK-7845: Biological and Pharmacological Profiling.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Comprehensive analysis of next generation sequencing and ARMS-PCR for detecting EGFR exon 20 insertion (ex20ins) mutations in Chinese non-small cell lung cancer patients.

Background: Amivantamab (JNJ-372) and mobocertinib (TAK-788) have been reported to have favorable therapeutic effect for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. Thus, accurate detection of EGFR ex20ins mutations is crucial for subsequent individualized therapy. The aim of this study was to compare the two common methods of next generation sequencing (NGS) and amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for detecting EGFR ex20ins mutations in Chinese NSCLC patients. Methods: We retrospectively analyzed EGFR mutations, especially for ex20ins, in 3,606 NSCLC patients detected by NGS and 1,785 patients by ARMS. Results: Among the 3,606 NGS patients, a total of 2,077 EGFR mutations and 95 EGFR ex20ins were identified, accounting for 57.6% and 2.6%, respectively. While 48.4% of EGFR mutations and 1.1% of ex20ins were detected in 1,785 ARMS patients, which were significantly lower than those of NGS (P<0.01). Thirty-four unique ex20ins variants were identified by NGS, and eight of them was reported for the first time. However, ARMS was designed to detect only several known EGFR ex20ins variants, and even did not include the most common variants in Chinese NSCLC patients. Conclusions: NGS is more advantageous and strongly recommended for the detection of EGFR ex20ins mutations. Considering the fast and cost-effective ARMS detection method, it is suggested that the primers design should be updated according to the characteristics of EGFR ex20ins mutations in Chinese NSCLC patients.

Cinnamaldehyde alleviates aspirin-induced gastric mucosal injury by regulating pi3k/akt pathway-mediated apoptosis, autophagy and ferroptosis.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. PURPOSE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3ß, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. CONCLUSION: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

ASS1 Enhances Anoikis Resistance via AMPK/CPT1A-mediated Fatty Acid Metabolism in Ovarian Cancer.

Metastasis is the leading cause of death in ovarian cancer (OC), with anoikis resistance being a crucial step for detached OC cells survival. Despite extensive research, targeting anoikis resistance remians a challenge. Here, we identify argininosuccinate synthase 1 (ASS1), a key enzyme in urea cycle, is markedly upregulated in OC cells in detached culture and is associated with increased anoikis resistance and metastasis. Disruption of the AMP/ATP balance by elevated ASS1 activates AMPK and its downstream factor, CPT1A. Then, ASS1 enhances FAO, leading to higher ATP generation and lipid utilization. Inhibition of CPT1A reverses ASS1-induced FAO. Our study gives some new functional insights into OC metabolism and represents a shift from traditional views, expanding ASS1's relevance beyond nitrogen metabolism to fatty acid metabolism. It uncovers how ASS1-induced FAO disrupts the AMP/ATP balance, leading to AMPK activation. By identifying the ASS1/AMPK/CPT1A axis as crucial for OC anoikis resistance and metastasis, our study opens up new avenues for therapeutic interventions.

Corrigendum: TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis after experimental subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fncel.2022.878673.].

Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances: a 3-month longitudinal study.

ABSTRACT: Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age-and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

The effects of childhood trauma on nonsuicidal self-injury and depressive severity among adolescents with major depressive disorder: The different mediating roles of positive and negative coping styles.

OBJECTIVE: We aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD). METHODS: The Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD. RESULTS: MDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (ß = 0.075, 95 % CI: 0.042-0.107) and ineffectiveness (ß = -0.084, 95 % CI: -0.160 âˆ¼ -0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (ß = 0.884, 95 % CI: 0.570-1.197), sexual abuse (ß = 0.825, 95 % CI: 0.527-1.124) and negative coping style (ß = 0.370, 95 % CI: 0.036-0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001-0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005-0.051) in adolescents with MDD. LIMITATIONS: A cross-sectional design, the retrospective self-reported data, the small sample size. CONCLUSION: Our findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents.

Size/Shape-Controllable Carbonized Wood Electrodes Enabled by an MXene Shell with Spatial Confinement and a Traction Effect on the Wood Cell Wall for Shape-Customizable Energy Storage Devices.

The shrinkage and collapse of wood cell walls during carbonization make it challenging to control the size and shape of carbonized wood (CW) through pre- or postprocessing (e.g., sawing, cutting, and milling). Herein, a shape-adaptive MXene shell (MS) is created on the surface of the wood cell walls. The MS limits the deformation of wood cell walls by spatial confinement and traction effects, which is supported by the inherent dimensional stability of the MS and the formation of new C-O-Ti covalent bonds between the wood cell wall and MS. Consequently, the volumetric shrinkage ratio of CW encapsulated by the MS (CW-MS) is significantly reduced from 54.8% for CW to 2.6% for CW-MS even at 800 °C. The harnessing of this collapse enables the production of CW-MS with prolonged stability and high electric conductivity (384 S m-1). These properties make CW-MS suitable for energy storage devices with various designed shapes, matching the increasingly compact and complex structures of electronic devices.

Characteristics and Clinical Value of MYC , BCL2, and BCL6 Rearrangement Detected by Next-generation Sequencing in DLBCL.

MYC , BCL2, and BCL6 rearrangements are clinically important events of diffuse large B-cell lymphoma (DLBCL). The ability and clinical value of targeted next-generation sequencing (NGS) in the detection of these rearrangements in DLBCL have not been fully determined. We performed targeted NGS (481-gene-panel) and break-apart FISH of MYC , BCL2, and BCL6 gene regions in 233 DLBCL cases. We identified 88 rearrangements (16 MYC ; 20 BCL2 ; 52 BCL6 ) using NGS and 96 rearrangements (28 MYC ; 20 BCL2 ; 65 BCL6 ) using FISH. The consistency rates between FISH and targeted NGS for the detection of MYC , BCL2, and BCL6 rearrangements were 93%, 97%, and 89%, respectively. FISH-cryptic rearrangements (NGS+/FISH-) were detected in 7 cases (1 MYC ; 3 BCL2 ; 2 BCL6 ; 1 MYC::BCL6 ), mainly caused by small chromosomal insertions and inversions. NGS-/FISH+ were detected in 38 cases (14 MYC ; 4 BCL2 ; 20 BCL6 ).To clarify the cause of the inconsistencies, we selected 17 from the NGS-/FISH+ rearrangements for further whole genome sequencing (WGS), and all 17 rearrangements were detected with break points by WGS. These break points were all located outside the region covered by the probe of targeted NGS, and most (16/17) were located in the intergenic region. These results indicated that targeted NGS is a powerful clinical diagnostics tool for comprehensive MYC , BCL2, and BCL6 rearrangement detection. Compared to FISH, it has advantages in describing the break point distribution, identifying uncharacterized partners, and detecting FISH-cryptic rearrangements. However, the lack of high-sensitivity caused by insufficient probe coverage is the main limitation of the current technology.

Microfluidic Digital Immunoassay for Point-of-Care Detection of NT-proBNP from Whole Blood.

The high prevalence and economic burden of heart failure remain a challenge to global health. This lifelong disease leads to a buildup of permanent heart damage, making early detection and frequent monitoring crucial for effective treatment. N-terminal proBNP (NT-proBNP) is an important biomarker for monitoring the disease state, but current commercial and research NT-proBNP assays require phlebotomy and bulky equipment or do not satisfy clinical requirements such as sensitivity and detection thresholds. Here, we report a point-of-care (POC) compatible microfluidic digital immunoassay that can quantify the NT-proBNP concentration in a small volume of whole blood. Our automated microfluidic device takes whole blood samples mixed with biotinylated detection antibodies and passes through a plasma filter to react with a capture antibody-functionalized sensor surface. Streptavidin-coated gold nanoparticles (GNPs) are then released to mark the surface-bound single NT-proBNP immunocomplexes and recorded with bright-field microscopy. NT-proBNP concentrations in the sample are quantified via a hybrid digital/analog calibration curve. Digital counts of bound GNPs are used as readout signal at low concentrations for high sensitivity detection, and GNP pixel occupancies are used at high concentrations for extended dynamic range. With this approach, we detected NT-proBNP in the range of 8.24-10 000 pg/mL from 7 µL of whole blood in 10 min, with a limit of detection of 0.94 pg/mL. Finally, the method was validated with 15 clinical serum samples, showing excellent linear correlation (r = 0.998) with Roche's Elecsys proBNP II assay. This evidence indicates that this method holds promise for decentralized monitoring of heart failure.

Functions of tensile and compressive strain on electronic and optical properties of B-doped monolayer arsenene.

CONTEXT: The structurals stability, electronic structure, density of states (DOS), and optical properties of B-doped arsenene under biaxial tensile and compressive strains were investigated using density functional theory (DFT) calculations. The doping system was found to exhibit good stability. The introduction of B atom transformed the originally indirect band gap of arsenene into a direct band gap. Under compressive strain, the band gap remained direct, gradually decreasing in value. In contrast, under tensile strain, the direct band gap occurred a transition into an indirect band gap, of which value initially increasing and then decreasing with an increasing strain. The static dielectric constant was increased under both compressive and tensile strains, but compressive strain had a stronger effect. Compressive strain led to an increase in the imaginary peak of the dielectric function, while tensile strain resulted in a decrease. Moreover, as compressive strain increased, the absorption and loss function peak initially blue-shifted and then red-shifted, while tensile strain caused a gradual red-shift of the absorption peak. METHOD: All DFT calculations were performed using Quantum Espresso software; the structures were optimized using generalized gradient approximation (GGA-PBE), and electronic structure and optical properties are performed using Heyd-Sceria-Ernzerhof (HSE06). The cut-off energy was set as 70 Ry, the Monkhorst-Pack grid was set to 10 × 10 × 1, the atomic convergence criterion was set as 1.0 × 10-6 Ry, and the convergence criterion of interatomic force was set as 1.0 × 10-4 Ry/Bohr.