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Case reportA 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed CDKN2A L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed.ConclusionChemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.

IntroductionMolecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre.MethodsPatients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014–2017) prior to institutional change to FoundationOne CDx (FM1; 2017–2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022.ResultsA total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN-altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75).ConclusionsBroad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS.

Abstract Cancer is one of the most life‐threatening diseases worldwide. Numerous diagnostic and therapeutic techniques, such as nanomaterials‐based cancer detection and imaging‐guided focal therapy, are successfully developed to achieve highly precise cancer theranostic strategies. However, due to unpredictive alterations occurring in cancer cell morphology, a lack of sensitivity and selectivity is a critical challenge among most biomarkers’ detection. To address this issue, instead of targeting proteins or biomarkers, the detection of cancer using whole cell‐based biosensors are ubiquitously discovered through a selective oligonucleotide, so‐called aptamer. Aptamer‐based whole‐cell detection is concurrently engaged with various nanomaterials, such as magnetic beads, gold (Au) nanoparticles, and graphene family to establish a better performance of the biosensor. In this research review, the recent strategies and prospects on whole‐cell cancer detection platform based on electrochemical aptasensors integrated with nanomaterials are thoroughly discussed and summarized. Finally, future challenges and prospects are also provided.

Type 2 diabetes mellitus (T2DM), the main type of diabetes, is a common chronic metabolic disease and a serious health concern worldwide. The aim of this study was to investigate the anti-diabetic effects and underlying mechanisms of pungent substances in Zanthoxylum armatum DC (ZA) fruit (PAZ), which are both edible and medicinal. We firstly investigated the possible molecular mechanisms of the PAZ on T2DM using network pharmacology and online databases. Furthermore, the predicted results were explored by Glucosamine induced AML12 experiments in vitro. After PAZ intervention, ROS levels decreased, MDA levels of oxidative stress indicators decreased, and SOD, GSH, and CAT levels increased compared to the model group. Thus, the pungent agents from the fruits of Z. armatum are beneficial for ameliorating type 2 diabetes mellitus via regulation of AMPK/PI3K/AKT signaling and reducing oxidative stress levels and exerting an anti-insulin resistance effect.

Estimating coastal ground deformation caused by ocean tidal loading (OTL) through time-series interferometric synthetic aperture radar (InSAR) techniques is challenging but achievable. Based on the two-dimensional wavelet decomposition method to extract spatial long-wavelength interferometric phases, the OTL deformation, residual orbital error, and atmospheric delay error hidden in long-wavelength phases can be isolated by independent component analysis. The ground OTL deformation in time-series InSAR phases is then accurately estimated using tidal harmonic functions. Experiments conducted with Sentinel-1 measurements in coastal areas reveal the following findings. Leveraging the blind source separation method allows for the effective extraction of high spatial resolution and large-scale ground OTL deformation correlation signals from the time-series InSAR phase. The differences between parameter values of main constituents estimated by the modeled InSAR ground OTL deformation and the FES2014b global tidal model range from 1.1% to 5.8%. Additionally, the difference in their predicted OTL deformation values is within the range of 0.9–4.9 mm. Compared to the FES2014b model correction method, the proposed approach removes OTL deformation from the time-series InSAR and results in a 26.1% reduction in the residual standard deviation value of ground deformation, which leads to a significant enhancement in the accuracy of ground deformation acquired for coastal areas. This work provides a novel approach to the theoretical research on OTL deformations, contributing to the refinement of InSAR ground deformation monitoring accuracy in coastal areas.

Sleep staging serves as a fundamental assessment for sleep quality measurement and sleep disorder diagnosis. Although current deep learning approaches have successfully integrated multimodal sleep signals, enhancing the accuracy of automatic sleep staging, certain challenges remain, as follows: 1) optimizing the utilization of multi-modal information complementarity, 2) effectively extracting both long- and short-range temporal features of sleep information, and 3) addressing the class imbalance problem in sleep data. To address these challenges, this paper proposes a two-stream encode-decoder network, named TSEDSleepNet, which is inspired by the depth sensitive attention and automatic multi-modal fusion (DSA2F) framework. In TSEDSleepNet, a two-stream encoder is used to extract the multiscale features of electrooculogram (EOG) and electroencephalogram (EEG) signals. And a self-attention mechanism is utilized to fuse the multiscale features, generating multi-modal saliency features. Subsequently, the coarser-scale construction module (CSCM) is adopted to extract and construct multi-resolution features from the multiscale features and the salient features. Thereafter, a Transformer module is applied to capture both long- and short-range temporal features from the multi-resolution features. Finally, the long- and short-range temporal features are restored with low-layer details and mapped to the predicted classification results. Additionally, the Lovász loss function is applied to alleviate the class imbalance problem in sleep datasets. Our proposed method was tested on the Sleep-EDF-39 and Sleep-EDF-153 datasets, and it achieved classification accuracies of 88.9% and 85.2% and Macro-F1 scores of 84.8% and 79.7%, respectively, thus outperforming conventional traditional baseline models. These results highlight the efficacy of the proposed method in fusing multi-modal information. This method has potential for application as an adjunct tool for diagnosing sleep disorders.

Abstract Background Our previous study in 2011 concluded that permissive underfeeding may improve outcomes in patients receiving parenteral nutrition therapy. This conclusion was tentative, given the small sample size. We conducted the present systematic review and trial sequential meta-analysis to update the status of permissive underfeeding in patients who were admitted to the intensive care unit (ICU). Methods Seven databases were searched: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and Cochrane Library. Randomized controlled trials (RCTs) were included. The Revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias in the enrolled trials. RevMan software was used for data synthesis. Trial sequential analyses (TSA) of overall and ICU mortalities were performed. Results Twenty-three RCTs involving 11,444 critically ill patients were included. There were no significant differences in overall mortality, hospital mortality, length of hospital stays, and incidence of overall infection. Compared with the control group, permissive underfeeding significantly reduced ICU mortality (risk ratio [RR] = 0.90; 95% confidence interval [CI], [0.81, 0.99]; P = 0.02; I2 = 0%), and the incidence of gastrointestinal adverse events decreased (RR = 0.79; 95% CI, [0.69, 0.90]; P = 0.0003; I2 = 56%). Furthermore, mechanical ventilation duration was reduced (mean difference (MD) = − 1.85 days; 95% CI, [− 3.44, − 0.27]; P = 0.02; I2 = 0%). Conclusions Permissive underfeeding may reduce ICU mortality in critically ill patients and help to shorten mechanical ventilation duration, but the overall mortality is not improved. Owing to the sample size and patient heterogeneity, the conclusions still need to be verified by well-designed, large-scale RCTs. Trial Registration The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD42023451308). Registered 14 August 2023

Abstract Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.

Abstract Background Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. Method Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. Results Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. Conclusion The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Abstract Background The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. Material and method Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. Results By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). Conclusions We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.

Abstract Background Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. population. The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. Methods Patients underwent gastrectomy for first primary GC in 2000–2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. Results Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. Conclusions Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors.

Abstract The limited surface coverage and activity of active hydrides on oxide surfaces pose challenges for efficient hydrogenation reactions. Herein, we quantitatively distinguish the long-puzzling homolytic dissociation of hydrogen from the heterolytic pathway on Ga2O3, that is useful for enhancing hydrogenation ability of oxides. By combining transient kinetic analysis with infrared and mass spectroscopies, we identify the catalytic role of coordinatively unsaturated Ga3+ in homolytic H2 dissociation, which is formed in-situ during the initial heterolytic dissociation. This site facilitates easy hydrogen dissociation at low temperatures, resulting in a high hydride coverage on Ga2O3 (H/surface Ga3+ ratio of 1.6 and H/OH ratio of 5.6). The effectiveness of homolytic dissociation is governed by the Ga-Ga distance, which is strongly influenced by the initial coordination of Ga3+. Consequently, by tuning the coordination of active Ga3+ species as well as the coverage and activity of hydrides, we achieve enhanced hydrogenation of CO2 to CO, methanol or light olefins by 4-6 times.

Abstract The effectiveness of sequence-to-sequence (seq2seq) models in natural language processing has been well-established over time, and recent studies have extended their utility by treating mathematical computing tasks as instances of machine translation and achieving remarkable results. However, our exploratory experiments have revealed that the seq2seq model, when employing a generic sorting strategy, is incapable of inferring on matrices of unseen rank, resulting in suboptimal performance. This paper aims to address this limitation by focusing on the matrix-to-sequence process and proposing a novel diagonal-based sorting. The method constructs a stable ordering structure of elements for the shared leading principal submatrix sections in matrices with varying ranks. We conduct experiments involving maximal independent sets and Sudoku laws, comparing seq2seq models utilizing different sorting methods. Our findings demonstrate the advantages of the proposed diagonal-based sorting in inference, particularly when dealing with matrices of unseen ranks. By introducing and advocating for this method, we enhance the suitability of seq2seq models for investigating the laws of matrix inclusion and exploring their potential in solving matrix-related tasks.

Abstract In this paper, a cost-effective and miniaturized instrument is proposed, which is based on a tunable modulated grating Y-branch (MG-Y) laser for rapid temperature measurement using a Fabry-Perot interferometer (FPI) sensor. The FPI sensor with a 1 463-µm cavity length is a short segment of a capillary tube sandwiched by two sections of single-mode fibers (SMFs). This system has a broad tunable range (1 527 nm–1 567 nm) with a wavelength interval of 8 pm and a tuning rate of 100 Hz. Temperature sensing experiments are carried out to investigate the performance of the system by demodulating the absolute cavity length of the FPI sensor using a cross-correlation algorithm. Experimental results show that the sensor can reach the response time as short as 94 ms with the sensitivity of 802 pm/°C. Benefiting from the homemade and integrated essential electrical circuits, the entire system has the small size, low cost, and practical application potential to be used in the harsh environment for rapid temperature measurement.