Stereodynamic control of nonadiabatic processes in low-energy Be+(2P) + H2 (v = 0, j = 2) collisions.

Controlling the relative arrangement of colliding molecules is crucial for determining the dynamical outcomes of chemical processes and has emerged as a hot spot of experimental research. Here, the quantum scattering calculations are conducted to investigate the stereodynamic control in collisions between Be+(2P) and H2 (v = 0, j = 2), which undergo nonadiabatic transitions to the electronic ground state. Stereodynamic preparation is achieved by controlling the initial alignment of the H2 bond axis relative to the scattering frame. For product BeH+ in the reactive process, the differential cross sections (DCSs) are significantly enhanced in the forward and sideways hemispheres when the alignment angle ß is 60°. For the product H2 in the quenching channel, the ß = 0° preparation can result in a more than one-fold increase in the DCS at a polar scattering angle of 0°. Furthermore, varying the alignment angle ß also has noteworthy effects on the rotational-state distributions of BeH+ products. Specifically, ß = 0° preparation can induce the disappearance of the bimodal distribution of rotational states at a collision energy of 0.05 eV.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

Theoretical study on photoinduced charge transfer in one-photon and two-photon absorption of branching oligofluorenes.

Oligofluorenes have been identified as very promising two-photon absorption (TPA) materials and present great application potential for the fabrication of nonlinear optical devices, but the TPA mechanism and corresponding electron excitation properties have not been studied. Here, the photoinduced charge transfer characteristics of V-shaped and Y-shaped branching oligofluorenes that consist of two and three fluorene units in each branch during one-photon absorption (OPA) and TPA processes are analyzed theoretically using the density functional theory and visualization sum-over-states model. The calculated results show that the OPA intensity and TPA cross-section are significantly enhanced by increasing the branch length or changing the structure from V-shaped to Y-shaped. The long-distance charge transfer only occurs on the second transition of TPA at high excited states. Compared to Y-shaped molecules, V-shaped structures exhibit a stronger cooperative effect among the different branches.

Unveiling Quantum Interference in the D+ + H2 Nonadiabatic Reaction Dynamics at Low Collision Energies.

Fully converged nonadiabatic dynamics calculations of the D+ + H2 → H+ + HD reaction are performed at low temperatures using the time-dependent wave packet approach based on a set of precise 3 × 3 diabatic potential energy surfaces (PESs) ( Phys. Chem. Chem. Phys., 2021, 23, 7735-7747, DOI: 10.1039/D0CP04100A). The D+ + H2 reaction is mediated by a dense manifold of resonances associated with the deep potential well on the ground-state PES. The calculated results show that the nonadiabatic coupling can affect the resonance positions, deviating from the expectation based solely on adiabatic considerations. Furthermore, significant forward-backward asymmetry in total differential cross sections (DCSs) is revealed, which is markedly influenced by nonadiabatic effects. The nonadiabatic effects not only affect the contribution of partial waves in the reaction but also make the interference patterns in the DCSs change significantly.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

Epsilon Class Glutathione S-Transferase Confers Phoxim Tolerance in the Black Cutworm Agrotis ipsilon (Lepidoptera: Noctuidae).

The black cutworm Agrotis ipsilon is a serious crop pest. Phoxim, an organophosphorus insecticide, has been widely used to control A. ipsilon. When phoxim is extensively applied, the susceptibility of A. ipsilon to insecticide is reduced. However, the mechanisms of tolerance of A. ipsilon to phoxim remain unclear. Herein, we report that an epsilon class glutathione S-transferase, AiGSTE1, confers phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim caused oxidative stress and activated the transcription of AiGSTe1 genes in A. ipsilon larvae. Recombinant AiGSTE1 expressed in Escherichia coli could metabolize phoxim. Furthermore, E. coli cells overexpressing AiGSTE1 displayed significant tolerance to oxidative stress. Knockdown of AiGSTe1 by RNA interference significantly increased the mortality of A. ipsilon larvae to phoxim. These results demonstrate that AiGSTE1 confers phoxim tolerance in A. ipsilon by metabolizing the insecticide and preventing phoxim-induced oxidative stress.

Lenvatinib Plus PD-1 Inhibitors versus Regorafenib in Patients with Advanced Hepatocellular Carcinoma After the Failure of Sorafenib: A Retrospective Study.

Purpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure. Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models. Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis. Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.

Sonoelastography for Testicular Tumor Identification: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy.

The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore®, PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies (n = 11) were eligible for data synthesis, nine of which (n = 9) utilized strain elastography and two (n = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits-risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors.

Computational Biomechanics of Sleep: A Systematic Mapping Review.

Biomechanical studies play an important role in understanding the pathophysiology of sleep disorders and providing insights to maintain sleep health. Computational methods facilitate a versatile platform to analyze various biomechanical factors in silico, which would otherwise be difficult through in vivo experiments. The objective of this review is to examine and map the applications of computational biomechanics to sleep-related research topics, including sleep medicine and sleep ergonomics. A systematic search was conducted on PubMed, Scopus, and Web of Science. Research gaps were identified through data synthesis on variants, outcomes, and highlighted features, as well as evidence maps on basic modeling considerations and modeling components of the eligible studies. Twenty-seven studies (n = 27) were categorized into sleep ergonomics (n = 2 on pillow; n = 3 on mattress), sleep-related breathing disorders (n = 19 on obstructive sleep apnea), and sleep-related movement disorders (n = 3 on sleep bruxism). The effects of pillow height and mattress stiffness on spinal curvature were explored. Stress on the temporomandibular joint, and therefore its disorder, was the primary focus of investigations on sleep bruxism. Using finite element morphometry and fluid-structure interaction, studies on obstructive sleep apnea investigated the effects of anatomical variations, muscle activation of the tongue and soft palate, and gravitational direction on the collapse and blockade of the upper airway, in addition to the airflow pressure distribution. Model validation has been one of the greatest hurdles, while single-subject design and surrogate techniques have led to concerns about external validity. Future research might endeavor to reconstruct patient-specific models with patient-specific loading profiles in a larger cohort. Studies on sleep ergonomics research may pave the way for determining ideal spine curvature, in addition to simulating side-lying sleep postures. Sleep bruxism studies may analyze the accumulated dental damage and wear. Research on OSA treatments using computational approaches warrants further investigation.

Diagnostic accuracy of circulating exosomal circRNAs in malignances: A meta-analysis and systematic review.

BACKGROUND: Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. RESULTS: Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies. CONCLUSIONS: In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.

Identification of 14 glutathione S-transferase genes from Lasioderma serricorne and characterization of LsGSTe1 involved in lambda-cyhalothrin detoxification.

In insects, glutathione S-transferases (GSTs) play a pivotal role in the detoxification of a wide range of pesticides. The cigarette beetle, Lasioderma serricorne, is an economically important pest insect of stored products. Recently, pyrethroid insecticides have been used to control this pest. However, little is known concerning the responses and functions of GSTs in L. serricorne under pyrethroid exposure. In this study, transcriptome sequencing was performed on L. serricorne, and a total of 14 GSTs were identified by retrieving the unigene dataset. Of these, 13 predicted GSTs fell into six cytosolic classes, namely, delta, epsilon, omega, sigma, theta, and zeta, and one was assigned to an "unclassified" group. The GST genes were differentially expressed in various larval tissues and at different developmental stages. Exposure to the pyrethroid insecticide lambda-cyhalothrin (LCT) caused oxidative stress in L. serricorne larvae and led to significantly elevated expression levels of six genes, among which LsGSTe1 was the most upregulated. Recombinant LsGSTE1 protein displayed LCT-metabolizing activity. Furthermore, LsGSTE1 protects cells against oxidative stress. Moreover, knockdown of LsGSTe1 by RNA interference dramatically increased the susceptibility of L. serricorne larvae to LCT treatment. The results from this study provide sequence resources and expression data for GST genes in L. serricorne. Our findings indicate that LsGSTE1 plays a dual role in LCT detoxification by metabolizing the pesticide and by preventing LCT-induced oxidative stress. Thus, the LsGSTe1 gene could be used as a potential target for sustainable management of the cigarette beetle.

Ultrasound-Guided Quadratus Lumborum Block at the Lateral Supra-Arcuate Ligament versus Subcostal Transversus Abdominis Plane Block for Postoperative Analgesia Following Open Hepatectomy: A Randomized Controlled Trial.

Purpose: Many studies confirmed that several approaches of quadratus lumborum block (QLB) were superior to transversus abdominis plane block (TAPB) in reducing opioid consumption during postoperative period. As a new QLB approach at the lateral supra-arcuate ligament (QLB-LSAL), the analgesic efficacy and safety in patients undergoing open hepatectomy are still unknown. This study aims to compare postoperative analgesia between the blocks in open hepatectomy. Patients and Methods: Sixty-two patients undergoing open hepatectomy were enrolled and randomly allocated into the QLB-LSAL group (group Q) and the subcostal TAPB group (group T). Preoperatively, patients received ultrasound-guided bilateral QLB-LSAL or subcostal TAPB with injection of 0.5% ropivacaine (a total volume of 40 mL). The primary outcome was cumulative total morphine equivalent consumption in the first postoperative 24 h. Other outcomes included numerical rating scale (NRS) scores at rest and coughing, cumulative total morphine equivalent consumption at 2, 6, 12, 48 h, Quality of Recovery-15 (QoR-15) scores, time to first patient-controlled intravenous analgesia (PCIA) request, time to first ambulation and adverse effects. Results: The cumulative total morphine equivalent consumption in group Q was decreased significantly at all postoperative time points (P < 0.01). The postoperative NRS scores at rest and coughing in group Q were lower than those in group T at all postoperative time points except 48 h (P < 0.05). A significant increase was also observed in the QoR-15 scores among patients in group Q. Time to first PCIA request was significantly prolonged in group Q than in group T, and time to first ambulation was shortened. Adverse effects showed no statistical significance between the two groups. Conclusion: Compared with subcostal TAPB, preoperative bilateral QLB-LSAL provided superior analgesic properties and promoted early postoperative recovery quality in patients undergoing open hepatectomy. Trial Registration: China Clinical Trials Registration Center (http://www.chictr.org.cn) ChiCTR2200063291, 3/9/2022.

Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients.

Background: Recent studies have shown that the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced under alkaline conditions. The purpose of this study is to assess the effect of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance among COVID-19 patients. Materials and methods: COVID-19 patients were recruited and randomly divided into two group, i.e., the experimental group and the control group. The experimental group received regular care plus nasal irrigation and oral rinse with 5% sodium bicarbonate solution, while the control group only received regular care. Nasopharyngeal and oropharyngeal swab samples were collected daily for reverse transcription-polymerase chain reaction (RT-PCR) assays. The negative conversion time and hospitalization time of the patients were recorded, and the results were statistically analyzed. Results: A total of 55 COVID-19 patients with mild or moderate symptoms were included in our study. There was no significant difference in gender, age and health status between the two groups. The average negative conversion time was 1.63 days after treatment with sodium bicarbonate, and the average hospitalization time of the control group and the experimental group were 12.53 and 7.7 days, respectively. Conclusions: Nasal irrigation and oral rinse with 5% sodium bicarbonate solution is effective in virus clearance for COVID-19 patients.

Deep Domain Adaptation Enhances Amplification Curve Analysis for Single-Channel Multiplexing in Real-Time PCR.

Data-driven approaches for molecular diagnostics are emerging as an alternative to perform an accurate and inexpensive multi-pathogen detection. A novel technique called Amplification Curve Analysis (ACA) has been recently developed by coupling machine learning and real-time Polymerase Chain Reaction (qPCR) to enable the simultaneous detection of multiple targets in a single reaction well. However, target classification purely relying on the amplification curve shapes faces several challenges, such as distribution discrepancies between different data sources (i.e., training vs testing). Optimisation of computational models is required to achieve higher performance of ACA classification in multiplex qPCR through the reduction of those discrepancies. Here, we proposed a novel transformer-based conditional domain adversarial network (T-CDAN) to eliminate data distribution differences between the source domain (synthetic DNA data) and the target domain (clinical isolate data). The labelled training data from the source domain and unlabelled testing data from the target domain are fed into the T-CDAN, which learns both domains' information simultaneously. After mapping the inputs into a domain-irrelevant space, T-CDAN removes the feature distribution differences and provides a clearer decision boundary for the classifier, resulting in a more accurate pathogen identification. Evaluation of 198 clinical isolates containing three types of carbapenem-resistant genes (blaNDM, blaIMP and blaOXA-48) illustrates a curve-level accuracy of 93.1% and a sample-level accuracy of 97.0% using T-CDAN, showing an accuracy improvement of 20.9% and 4.9% respectively. This research emphasises the importance of deep domain adaptation to enable high-level multiplexing in a single qPCR reaction, providing a solid approach to extend qPCR instruments' capabilities in real-world clinical applications.

Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy.

Previous studies suggest that baclofen may be useful in the treatment of intractable hiccup caused by chemotherapy. This study was aimed to assess the possible efficacy and safety of baclofen. In total, 65 patients with intractable hiccup caused by chemotherapy were screened. 45 patients with intractable hiccup caused by chemotherapy were finally recruited. Participants in the trial received 10 mg baclofen three times daily for 3 days. The primary outcome measure was cessation of hiccups. Secondary outcome measures included efficacy and adverse events. All 45 patients completed the study. Among them, 41 cases were cured (91.11%, 41/45), 4 cases were relieved (8.89%, 4/45), and the overall effective rate was 100% (45/45). Furthermore, the median remission time was 2(1, 9) times, the median cure time was 2(1, 9) times, the remission rate of one-time was 13.33% (6/45), the remission rate of two-time was 53.33% (24/45), and 2 cases (4.44%, 2/45) relapsed after drug withdrawal. No serious adverse events were documented. Only 1 case (2.22%) had grade 2 fatigue and 2 cases (4.44%) had grade 1 sleepiness. Baclofen is safe and effective in the treatment of intractable hiccup caused by chemotherapy of malignant tumor.

Vision Transformers (ViT) for Blanket-Penetrating Sleep Posture Recognition Using a Triple Ultra-Wideband (UWB) Radar System.

Sleep posture has a crucial impact on the incidence and severity of obstructive sleep apnea (OSA). Therefore, the surveillance and recognition of sleep postures could facilitate the assessment of OSA. The existing contact-based systems might interfere with sleeping, while camera-based systems introduce privacy concerns. Radar-based systems might overcome these challenges, especially when individuals are covered with blankets. The aim of this research is to develop a nonobstructive multiple ultra-wideband radar sleep posture recognition system based on machine learning models. We evaluated three single-radar configurations (top, side, and head), three dual-radar configurations (top + side, top + head, and side + head), and one tri-radar configuration (top + side + head), in addition to machine learning models, including CNN-based networks (ResNet50, DenseNet121, and EfficientNetV2) and vision transformer-based networks (traditional vision transformer and Swin Transformer V2). Thirty participants (n = 30) were invited to perform four recumbent postures (supine, left side-lying, right side-lying, and prone). Data from eighteen participants were randomly chosen for model training, another six participants' data (n = 6) for model validation, and the remaining six participants' data (n = 6) for model testing. The Swin Transformer with side and head radar configuration achieved the highest prediction accuracy (0.808). Future research may consider the application of the synthetic aperture radar technique.

Endocrine Tumor Classification via Machine-Learning-Based Elastography: A Systematic Scoping Review.

Elastography complements traditional medical imaging modalities by mapping tissue stiffness to identify tumors in the endocrine system, and machine learning models can further improve diagnostic accuracy and reliability. Our objective in this review was to summarize the applications and performance of machine-learning-based elastography on the classification of endocrine tumors. Two authors independently searched electronic databases, including PubMed, Scopus, Web of Science, IEEEXpress, CINAHL, and EMBASE. Eleven (n = 11) articles were eligible for the review, of which eight (n = 8) focused on thyroid tumors and three (n = 3) considered pancreatic tumors. In all thyroid studies, the researchers used shear-wave ultrasound elastography, whereas the pancreas researchers applied strain elastography with endoscopy. Traditional machine learning approaches or the deep feature extractors were used to extract the predetermined features, followed by classifiers. The applied deep learning approaches included the convolutional neural network (CNN) and multilayer perceptron (MLP). Some researchers considered the mixed or sequential training of B-mode and elastographic ultrasound data or fusing data from different image segmentation techniques in machine learning models. All reviewed methods achieved an accuracy of ≥80%, but only three were ≥90% accurate. The most accurate thyroid classification (94.70%) was achieved by applying sequential training CNN; the most accurate pancreas classification (98.26%) was achieved using a CNN-long short-term memory (LSTM) model integrating elastography with B-mode and Doppler images.

Efficacy and Safety of Regorafenib with or without PD-1 Inhibitors as Second-Line Therapy for Advanced Hepatocellular Carcinoma in Real-World Clinical Practice.

Background: Regorafenib is the first oral targeted drug as a second-line agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. Recently, several studies demonstrated that the combination of regorafenib and PD-1 inhibitors showed a synergistic effect. Our study aimed to evaluate the efficacy of regorafenib with PD-1 inhibitors (RP) and regorafenib alone (R) as second-line treatment for advanced HCC. Methods: From October 2018 to January 2022, our retrospective study evaluated advanced HCC patients who received regorafenib with PD-1 inhibitors or regorafenib alone as a second-line treatment at the Second Affiliated Hospital of Nanchang University, China. The efficacy and safety were compared between RP and R groups. Results: In total, 78 patients were enrolled in our study and were separated into two groups - RP group (48) and R group (30) - according to the criteria. The ORR of RP group and R group was 18.8% and 10%, respectively, and the DCR was 66.7% and 43.3%, respectively. The RP group had a longer mPFS (5.9 months vs 3.0 months, P<0.001) and mOS (12.9 months vs 10.3 months, P=0.010) than the R group. Regorafenib monotherapy is an independent prognostic factor for OS and PFS. In OS, subgroup analysis showed that patients with AFP ≥ 400ng/mL, BCLC C stage and extrahepatic metastasis may benefit from RP, while in PFS, subgroup analysis showed that patients with BCLC C stage, AFP ≥ 400ng/mL, extrahepatic metastasis, ALBI ≥-2.60 and first-line treatment of sorafenib may benefit from RP. The incidence of grade 3/4 adverse reaction in the two groups was 22.9% and 23.3%, respectively, with no significant statistically difference (P=0.966). Conclusion: In the second-line therapy of advanced HCC, compared to regorafenib alone, the combination of regorafenib and PD-1 inhibitors showed promising efficacy and tolerable drug toxicity.

Depth-Camera-Based Under-Blanket Sleep Posture Classification Using Anatomical Landmark-Guided Deep Learning Model.

Emerging sleep health technologies will have an impact on monitoring patients with sleep disorders. This study proposes a new deep learning model architecture that improves the under-blanket sleep posture classification accuracy by leveraging the anatomical landmark feature through an attention strategy. The system used an integrated visible light and depth camera. Deep learning models (ResNet-34, EfficientNet B4, and ECA-Net50) were trained using depth images. We compared the models with and without an anatomical landmark coordinate input generated with an open-source pose estimation model using visible image data. We recruited 120 participants to perform seven major sleep postures, namely, the supine posture, prone postures with the head turned left and right, left- and right-sided log postures, and left- and right-sided fetal postures under four blanket conditions, including no blanket, thin, medium, and thick. A data augmentation technique was applied to the blanket conditions. The data were sliced at an 8:2 training-to-testing ratio. The results showed that ECA-Net50 produced the best classification results. Incorporating the anatomical landmark features increased the F1 score of ECA-Net50 from 87.4% to 92.2%. Our findings also suggested that the classification performances of deep learning models guided with features of anatomical landmarks were less affected by the interference of blanket conditions.

A thioredoxin peroxidase protects Pieris rapae from oxidative stress induced by chlorantraniliprole exposure.

Chlorantraniliprole (CAP) is an insecticide widely used to control the small white butterfly (SWB), Pieris rapae. Exposure to CAP can cause oxidative injury in SWB; however, it is unclear if antioxidant enzymes are involved in the defense process. In this study, a thioredoxin peroxidase (PrTPX1) gene was identified from SWB by using a homology search method. The gene encoded a 195 amino-acid PrTPX1 protein. Sequence characteristics and phylogenetic analysis indicated that PrTPX1 was a typical "2-Cys" TPX, and the PrTPX1 gene consisted of four exons and three introns. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the messenger RNA levels of PrTPX1 were highest in third-, fourth- and fifth-instar larval stages and in the larval midgut. Treatment with sublethal doses (LD20 and LD50 ) of CAP for 6, 12, 18, and 24 h resulted in increased H2 O2 concentration in SWB larvae, indicating insecticide-induced oxidative stress. The transcriptional levels of PrTPX1 were significantly enhanced in larvae exposed to CAP. Recombinant PrTPX1 protein was expressed in Escherichia coli. Enzymatic assay revealed that the protein displayed antioxidant activity and was able to protect against oxidative challenge. These results indicated that PrTPX1 plays an important role in oxidative stress responses and may contribute to the CAP tolerance in SWB.