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Abstract Background Postoperative liver metastasis significantly impacts the prognosis of pancreatic neuroendocrine tumor (panNET) patients after R0 resection. Combining computational pathology and deep learning radiomics can enhance the detection of postoperative liver metastasis in panNET patients. Methods Clinical data, pathology slides, and radiographic images were collected from 163 panNET patients post-R0 resection at Fudan University Shanghai Cancer Center (FUSCC) and FUSCC Pathology Consultation Center. Digital image analysis and deep learning identified liver metastasis-related features in Ki67-stained whole slide images (WSIs) and enhanced CT scans to create a nomogram. The model’s performance was validated in both internal and external test cohorts. Results Multivariate logistic regression identified nerve infiltration as an independent risk factor for liver metastasis (p

Abstract In recent years, most video segmentation methods use deep CNN to process the input image, but they did not fully mine the rich intermediate predictions in spatio‐temporal space. And, the segmentation challenges such as occlusion, severe deformation and illumination have not been well solved so far. To alleviate these problems, this paper focuses on constructing multi module network structures that represent multi semantics and proposes a video object segmentation network via coupled‐stream architecture with feature memory mechanism. This network first extracts high‐level semantic features, edge features, long‐term and short‐term stable depth features of the target, and then decode them into the segmentation mask of target. In addition, negative skeleton inhibition and frame interpolation are used to prevent the interference of similar objects and motion blur, respectively. The method has a low GPU memory usage, regardless of the number of object in video. And performs 86.5%and 62.4% in J&F measure on DAVIS 2016 and DAVIS 2017 validation set, without fine‐tuning and online training.

Summary: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

IntroductionThe immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro.MethodTo test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses.ResultsThe stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes.DiscussionThese in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.

Purpose: In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. Methods and Materials: We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. Results: From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Conclusions: Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.

Background: Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR. To address this, we investigated the effect of GLP-1RA-based treatment strategies on TIR among patients with T2DM in real-world clinical practice.Methods: This multicenter, retrospective, real-world study included patients with T2DM who had previously used a continuous glucose monitoring (CGM) system and received treatment with GLP-1RAs or oral antidiabetic drugs (OADs). Patients who received OADs served as controls and were matched in a 1:1 ratio to their GLP-1RA counterparts by propensity score matching. The primary endpoint was the TIR after 3–6 months of treatment.Results: According to propensity score matching, 202 patients were equally divided between the GLP-1RA and OAD groups. After 3–6 months of treatment, the TIR values for the GLP-1RA and OAD groups were 76.0% and 65.7%, respectively (p < 0.001). The GLP-1RA group displayed significantly lower time above range (TAR) and mean glucose values than the OAD group (p < 0.001). Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3–6 months of treatment (p < 0.05).Conclusion: These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA.Clinical trial registration:http://www.chinadrugtrials.org.cn/index.html, identifier number ChiCTR2300073697.

Abstract ‘Fingerprint’ identification is the key to turquoise provenance studies, but previous studies have met with limited success in China. Turquoises in China mainly occur in altered sedimentary rocks and are formed by weathering, leaching and sedimentation. This paper evaluates the potential for sedimentary environment sensitive elements to be used to distinguish between turquoise deposits in China. In this paper, the ratios of V/Mo, Ce/Ce*, Ni/Co, Sr/Ba, Tl/Ga, Li/Ba and V/Cr were calculated for turquoise of different origins. Our results show that these parameters when used alongside Ga concentration permit effective discrimination between turquoise sources in China. This approach brings to light a new means of analyzing trace element databases and an untapped wealth of information that can be used for future turquoise provenance studies.

Abstract Background Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients. Methods A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach’s alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value. Results The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach’s alpha coefficient of the C-TSFI was 0.861, Cronbach’s alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904–0.96, P

Abstract The current instance segmentation method can achieve satisfactory results in common scenarios. However, under the overlap or partial occlusion between targets caused by the complex scenes, accurate segmentation of pigs remains a challenging task. To address the problem, the authors propose an instance segmentation method based on Mask Scoring region‐based convolutional neural networks (R‐CNN) (MS R‐CNN), which creates the adversarial network called MaskDis in the head branch of MS R‐CNN. The MaskDis is trained as a discriminator using a generative adversarial network, and the MS R‐CNN model is used as a generator during model training. The adversarial training enables the generator to learn context information and features at the pixel level, which effectively improves the segmentation quality under pigs’ overlapping or dense occlusions scenes. Experimental conducted on the pig object segmentation dataset show that the proposed approach achieves a precision of 92.03%, a recall of 92.18%, and an F1 score of 0.9210. Compared with the basic MS R‐CNN model, the approach achieved a 2.25% improvement in precision and 1.18% improvement in F1 score. Furthermore, the improved approach outperformed advanced instance segmentation methods such as YOLACT, Swin Transformer, YOLOv5‐seg, and SOLOv2 on COCO evaluation metrics. These experimental results demonstrate the effectiveness of the proposed approach in instance segmentation of pigs in complex scenes, providing technical support for non‐contact pig automatic management.

Pig behavioral analysis based on multi-object tracking (MOT) technology of surveillance videos is vital for precision livestock farming. To address the challenges posed by uneven lighting scenes and irregular pig movements in the MOT task, we proposed a pig MOT method named RpTrack. Firstly, RpTrack addresses the issue of lost tracking caused by irregular pig movements by using an appropriate Kalman Filter and improved trajectory management. Then, RpTrack utilizes BIoU for the second matching strategy to alleviate the influence of missed detections on the tracking performance. Finally, the method utilizes post-processing on the tracking results to generate behavioral statistics and activity trajectories for each pig. The experimental results under conditions of uneven lighting and irregular pig movements show that RpTrack significantly outperforms four other state-of-the-art MOT methods, including SORT, OC-SORT, ByteTrack, and Bot-SORT, on both public and private datasets. The experimental results demonstrate that RpTrack not only has the best tracking performance but also has high-speed processing capabilities. In conclusion, RpTrack effectively addresses the challenges of uneven scene lighting and irregular pig movements, enabling accurate pig tracking and monitoring of different behaviors, such as eating, standing, and lying. This research supports the advancement and application of intelligent pig farming.

ABSTRACTPatients with hematologic malignancies are often immunodeficient and therefore have a higher risk of severe symptoms from coronavirus disease 2019 (COVID-19). We retrospectively examined a cohort of 289 patients from 16 hospitals in Zhejiang Province who had hematologic malignancies and COVID-19 during a period when the Omicron variant was predominant. Univariate analysis showed that some clinical characteristics, including elder age (P = 0.014), multiple comorbid conditions (P = 0.011), and receipt of active antineoplastic therapy (P = 0.018) were associated with an increased risk of severe COVID-19. Patients with severe/critical COVID-19 had significantly lower levels of lymphocytes and serum albumin, and significantly higher levels of D-dimer, lactate dehydrogenase, C-reactive protein, and interleukin-6 (all P

Choristoneura metasequoiacola Liu, 1983 is an important caterpillar species that specifically infests the leaves and branches of Metasequoia glyptostroboides Hu & W. C. Cheng 1948 with short larval infestations, long-term dormancy, and has a limited distribution in Lichuan, Hubei, China. The complete mitochondria genome of C. metasequoiacola was determined by using Illumina NovaSeq, and analyzed based on previously annotated sibling species. In total, we obtained mitochondria genome with 15,128 bp in length, circular in shape with a double-stranded closed ring structure, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and an AT-rich region. Of which the nucleotide composition was highly A + T biased, accounting for 81.98% of the whole mitogenome. Thirteen protein-coding genes (PCGs) were 11,142 bp; Twenty-two tRNA genes and AT-rich region were 1,472 and 199 bp, respectively. Phylogenetically, the relationship between Choristoneura spp. (containing C. metasequoiacola) and Adoxophyes spp. was closer than any other two genera from Tortricidae, and the relationship between C. metasequoiacola and C.murinana was the closest among nine sibling species from that genus, which helps to explain species evolution within the family Tortricidae.

Abstract Color pencil drawing is well-loved due to its rich expressiveness. This paper proposes an approach for generating feature-preserving color pencil drawings from photographs. To mimic the tonal style of color pencil drawings, which are much lighter and have relatively lower saturation than photographs, we devise a lightness enhancement mapping and a saturation reduction mapping. The lightness mapping is a monotonically decreasing derivative function, which not only increases lightness but also preserves input photograph features. Color saturation is usually related to lightness, so we suppress the saturation dependent on lightness to yield a harmonious tone. Finally, two extremum operators are provided to generate a foreground-aware outline map in which the colors of the generated contours and the foreground object are consistent. Comprehensive experiments show that color pencil drawings generated by our method surpass existing methods in tone capture and feature preservation.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

The Middle Jurassic sandstone reservoirs of the Turpan-Hami Basin are the main targets for unconventional tight oil and gas exploration and development.To better understanding the main controlling factors of pore characteristics in the Middle Jurassic tight sandstones of the Shengbei Sag, Turpan-Hami Basin, a comprehensive investigation referring to lithology, diagenesis, physical properties, and pore structure was conducted on samples obtained from 8 wells. The results indicate that the Middle Jurassic tight sandstone reservoir characterized by low porosity and ultralow permeability primarily contains feldspar lithic sandstones, followed by lithic sandstones.These sandstone reservoirs suffered strong compaction and complicated mineral cementation, replacement, and dissolution. These sandstone reservoirs are dominated by the secondary pores generated by feldspar dissolution, with some residual interparticle pores, quartz dissolution pores, clay mineral interlayer pores, and microfractures.Pore throat of 5-50 nm most widely appears in these reservoirs, while the porosity and permeability of these reservoirs mainly depend on the pore throats of 50 nm-1 μm and 100-800 μm, as indicated by the good positive correlations between pore throats and volumes. Both porosity and permeability correlate positively with the quartz and feldspar contents but negatively with the clay and carbonate contents. These correlations were supposed to be caused by two factors: ①strong compaction led to the loss of most interparticle pores but kept the residual interparticle pores associated with rigid quartz, and caused the occurrence of microfractures and dissolution pores within the quartz; the migration of hydrocarbon fluids containing organic acids into the Middle Jurassic reservoirs resulted in the significant dissolution of feldspar and generation of secondary dissolution pores. This process promoted theoccurrence of pore throats of 50 nm-1 μm and 100-800 μm and improved the porosity and permeability. ②The primary interparticle pores and secondary microfractures were filled with authigenic clay or carbonate cement; the replacement of feldspar by calcite disturbed the positive effects of feldspar dissolution on the porosity and permeability, which reduced the occurrence of 50 nm-1 μm and 100-800 μm pore throats and the physical properties of these reservoirs.Therefore, the occurrence of pores was closely related to the early sedimentary environments and the later diagenesis after deposition.More importantly, mechanical compaction, feldspar dissolution, and authigenic mineral cementation played crucial roles in regulating the occurrence of pores and the physical properties of these sandstone reservoirs in the study area.This study should be helpful in predicting the favorable exploration areas of tight oil and gas in the Middle Jurassic sandstone reservoirs in the Shengbei Sag, Turpan-Hami Basin.

On the southeastern margin of the Ordos Basin, the mineral composition of marine-continent transitional facies deposits is complex. The shale, sandstone, coal, and related lithofacies frequently interact, and the lithology changes rapidly in the vertical direction. Due to the low resolution of conventional logging method and borehole enlargement which is a common while drilling, the commonly used methods for identification of lithology including high-quality shale which is prevailing in marine shale gas evaluation are less effective for the study area. First, deconvolution technology was used to improve the resolution of natural gamma rays, gamma rays without uranium and uranium logging curves. Then, a log cross-plot was used to identify the lithology including shale of marine-continent transitional facies, and the uranium-spontaneous potential curve overlap method was proposed to identify high-quality shale from marine-continent transitional facies. The results show that the deconvolution method can effectively improve the vertical resolution of natural gamma rays, gamma rays without uranium and uranium logging curves. The cross-plot of natural gamma-density logging data has a better effect on identifying the lithology of the marine-continent transitional facies, and the cross-plot of uranium logging data and gamma ray data without uranium can further identify three types of shale lithofacies (calcareous siliceous shale, siliceous clay shale and clay shale). In the marine-continent transitional facies, the newly proposed uranium-spontanous potential overlap method is better than the traditional ΔlogR method inidentifying high-quality shale. This research can provide theoretical support for reservoir evaluation of marine-continent transitional shale gas and improve the accuracy of high-quality shale identification.

Abstract Background TP53 mutations are frequent in non‐small cell lung cancer (NSCLC). Different categories of TP53 mutations may be associated with survival in advanced NSCLC, but their effect on prognosis is diverse. To date, a comprehensive comparison of the relationship between different classes of TP53 alterations and survival in advanced NSCLC has rarely been performed. Moreover, the prognostic significance of a novel approach called the evolutionary action of TP53 (EAp53) in advanced NSCLC is unclear. Methods A total of 210 patients with NSCLC harboring TP53 mutation data were enrolled. Genomic and clinical data for the Memorial Sloan Kettering Cancer Center (MSKCC) cohort with advanced NSCLC were obtained from cBioPortal. Relationship between clinical characteristics and TP53 mutations was performed by Fisher's exact test or χ2 test. Overall survival (OS) analysis was evaluated using Kaplan–Meier method and Cox proportional hazards regression model. Results TP53 mutations were identified in 51.4% of NSCLC patients and were mainly located in exons 5, 7, and 8. The distribution patterns of missense and truncating mutations of TP53 were remarkably different. Among patients with advanced NSCLC who never received immune checkpoint inhibitor treatments, EAp53 high‐risk mutations were significantly associated with poor OS in both our cohort and the MSKCC cohort. Moreover, marked differences were observed in the mutational landscape between patients with EAp53 high‐risk mutations (HR group) and other patients (OT group). The HR group displayed higher mutation frequencies in the RTK, cell cycle, and DNA damage repair (DDR) pathways than the OT group. In addition, the tumor mutation burden in the HR group was significantly higher than that in the OT group. Conclusions This study provided important insights into the molecular‐clinical profile of TP53‐mutated NSCLC patients. Moreover, the data revealed that EAp53 high‐risk mutations were an independent prognostic factor for worse OS in advanced NSCLC.

Cryptomeria japonica var. sinensis Miquel in south China is currently overwhelmingly infested by a native caterpillar species, Dendrolimus houi (Lepidoptera), which is causing severe economic losses and ecological disasters in both planted and natural forests. Our results include report of five parasitoid species and eight parasitoid flies within D. houi and a dominant endoparasitoid species Kriechbaumerella dendrolimi, which attacks pupae of D. houi with a high parasitism rate. This result might be helpful to improve better identification and application in the future for potential biological control of D. houi in the forests of east Asia.

ObjectiveOur previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects.MethodsWe designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms.ResultsWe found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β signaling pathway.ConclusionThe combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.

Background & Aims: Distinct vascular patterns, including microvascular invasion (MVI) and vessels encapsulating tumour clusters (VETC), are associated with poor outcomes of hepatocellular carcinoma (HCC). Imaging surrogates of these vascular patterns potentially help to predict post-resection recurrence. Herein, a prognostic model integrating imaging-based surrogates of these distinct vascular patterns was developed to predict postoperative recurrence-free survival (RFS) in patients with HCC. Methods: Clinico-radiological data of 1,285 patients with HCC from China undergoing surgical resection were retrospectively enrolled from seven medical centres between 2014 and 2020. A prognostic model using clinical data and imaging-based surrogates of MVI and VETC patterns was developed (n = 297) and externally validated (n = 373) to predict RFS. The surrogates (i.e. MVI and VETC scores) were individually built from preoperative computed tomography using two independent cohorts (n = 360 and 255). Whether the model's stratification was associated with postoperative recurrence following anatomic resection was also evaluated. Results: The MVI and VETC scores demonstrated effective performance in their respective training and validation cohorts (AUC: 0.851–0.883 for MVI and 0.834–0.844 for VETC). The prognostic model incorporating serum alpha-foetoprotein, tumour multiplicity, MVI score, and VETC score achieved a C-index of 0.748–0.764 for the developing and external validation cohorts and generated three prognostically distinct strata. For patients at model-predicted medium risk, anatomic resection was associated with improved RFS (p 0.05). Conclusions: The proposed model integrating imaging-based surrogates of distinct vascular patterns enabled accurate prediction for RFS. It can potentially be used to identify HCC surgical candidates who may benefit from anatomic resection. Impact and implications: MVI and VETC are distinct vascular patterns of HCC associated with aggressive biological behaviour and poor outcomes. Our multicentre study provided a model incorporating imaging-based surrogates of these patterns for preoperatively predicting RFS. The proposed model, which uses imaging detection to estimate the risk of MVI and VETC, offers an opportunity to help shed light on the association between tumour aggressiveness and prognosis and to support the selection of the appropriate type of surgical resection.

Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). With increasing approval of CAR T-cell products and advances in CAR T cell therapy, CAR T cells are expected to be used in a growing number of cases. However, CAR T-cell-associated toxicities can be severe or even fatal, thus compromising the survival benefit from this therapy. Standardizing and studying the clinical management of these toxicities are imperative. In contrast to other hematological malignancies, such as acute lymphoblastic leukemia and multiple myeloma, anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features, most notably local cytokine-release syndrome (CRS). However, previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL. Consequently, we developed this consensus for the prevention, recognition, and management of these toxicities, on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions. This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management, and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Abstract The knowledge of body size/weight is necessary for the general growth enhancement of swine as well as for making informed decisions that concern their health, productivity, and yield. Therefore, this work aims to automate the collection of pigs’ body parameters using images from Kinect V2 cameras, and the development of Multilayer Perceptron Neural Network (MLP NN) models to predict their weight. The dataset obtained using 3D light depth cameras contains 9980 pigs across the S21 and S23 breeds, and then grouped into 70:15:15 training, testing, and validation sets, respectively. Initially, two MLP models were built and evaluations revealed that model 1 outperformed model 2 in predicting pig weights, with root mean squared error (RMSE) values of 5.5 and 6.0 respectively. Moreover, employing a normalized dataset, two new models (3 and 4) were developed and trained. Subsequently, models 2, 3, and 4 performed significantly better with a RMSE value of 5.29 compared to model 1, which has a RMSE value of 6.95. Model 3 produced an intriguing discovery i.e. accurate forecasting of pig weights using just two characteristics, age and abdominal circumference, and other error values show corresponding results

Feeder cells play an important role in the culture of human pluripotent stem cells (hPSCs) in vitro. Previously, we used methanol as a fixative to prepare feeder cells for the cultivation of pluripotent stem cells (PSCs), and this method could maintain the self‐renewal and pluripotency of PSCs. However, methanol is toxic, and so here we examined whether ethanol could be used to prepare feeder cells as a fixative for hPSC culturing. Primed, naïve, and extended human embryonic stem cells and induced pluripotent stem cells can maintain self‐renewal and undifferentiated potential on feeder cells treated with ethanol for an extended period. RNA sequencing analysis showed that the expression of collagen‐related genes in hPSCs cultured on feeder cells treated with ethanol was significantly lower as compared with hPSCs cultured on feeder cells treated with mitomycin C. Therefore, we speculate that the signaling pathway mediated by collagen‐related genes may, at least in part, contribute to the maintenance of self‐renewal and pluripotency of PSCs induced by feeder cells treated with chemicals.

Abstract Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3–4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

The role of sea surface temperature (SST) variability in the boreal winter intraseasonal oscillation (ISO) over the tropical Indian Ocean (TIO) is investigated in this study using the Community Earth System Model Version 2. An atmospheric general coupled model (AGCM) run forced by daily SSTs derived from a parallel coupled circulation model (CGCM) run is compared with reanalysis and the original coupled simulation. The comparison of atmospheric-coupled GCMs reveals the frequency and spatial tendency of the SST effect on the atmospheric ISO. The 50–80 d component of the ISO over the TIO is significantly intensified in the AGCM run. The SST-to-atmosphere effect is most prominent over the southeastern TIO. In the AGCM run, low-level wind anomalies related to SST appear west of the ISO convection center, contrasting with the previous findings that the SST effect appears east of the convection center.

Citrus fruits hold pivotal positions within the agricultural sector. Accurate yield estimation for citrus fruits is crucial in orchard management, especially when facing challenges of fruit occlusion due to dense foliage or overlapping fruits. This study addresses the issues of low detection accuracy and the significant instances of missed detections in citrus fruit detection algorithms, particularly in scenarios of occlusion. It introduces AG-YOLO, an attention-based network designed to fuse contextual information. Leveraging NextViT as its primary architecture, AG-YOLO harnesses its ability to capture holistic contextual information within nearby scenes. Additionally, it introduces a Global Context Fusion Module (GCFM), facilitating the interaction and fusion of local and global features through self-attention mechanisms, significantly improving the model’s occluded target detection capabilities. An independent dataset comprising over 8000 outdoor images was collected for the purpose of evaluating AG-YOLO’s performance. After a meticulous selection process, a subset of 957 images meeting the criteria for occlusion scenarios of citrus fruits was obtained. This dataset includes instances of occlusion, severe occlusion, overlap, and severe overlap, covering a range of complex scenarios. AG-YOLO demonstrated exceptional performance on this dataset, achieving a precision (P) of 90.6%, a mean average precision (mAP)@50 of 83.2%, and an mAP@50:95 of 60.3%. These metrics surpass existing mainstream object detection methods, confirming AG-YOLO’s efficacy. AG-YOLO effectively addresses the challenge of occlusion detection, achieving a speed of 34.22 frames per second (FPS) while maintaining a high level of detection accuracy. This speed of 34.22 FPS showcases a relatively faster performance, particularly evident in handling the complexities posed by occlusion challenges, while maintaining a commendable balance between speed and accuracy. AG-YOLO, compared to existing models, demonstrates advantages in high localization accuracy, minimal missed detection rates, and swift detection speed, particularly evident in effectively addressing the challenges posed by severe occlusions in object detection. This highlights its role as an efficient and reliable solution for handling severe occlusions in the field of object detection.

Osteosarcoma (OS) is the most frequent primary malignant bone tumor. Ferroptosis, a form of regulated cell death, is a key tumor suppression mechanism. Although methionine adenosyltransferase II alpha (MAT2A) has been reported to inhibit several tumor cells, it is unclear whether inhibition of MAT2A in OS cells can reduce ferroptosis. CCK-8, flow cytometry, and Transwell assays were performed to evaluate cell viability, cell apoptosis/cycle, and cell migration, respectively. The levels of ferrous iron and glutathione (GSH) levels in cells were measured to evaluate the degree of cell ferroptosis. Western blot analysis was performed to detect protein levels of MAT2A, p-STAT3 (Ser727)/STAT3, and solute carrier family 7 member 11 (SLC7A11) in OS cells. MAT2A was significantly upregulated in OS specimens and high MAT2A expression was associated with a poorer prognosis in OS patients. shRNA targeting MAT2A significantly increased OS cell apoptosis, triggered cell cycle arrest in the G2 phase, and attenuated migration ability in vitro. MAT2A depletion dramatically inhibited tumor progression of OS in vivo. Overexpression of MAT2A rescued the tumor inhibition caused by miR-26b-5p. MAT2A knockdown promoted OS cell ferroptosis. miR-26b-5p/MAT2A regulates tumor malignant progression and OS cell ferroptosis by controlling p-STAT3 and SLC7A11 expressions. Taken together, our study displayed that miR-26b-5p/MAT2A triggers ferroptosis in OS cells by increasing intracellular ferrous iron levels and inhibiting the STAT3/SLC7A11 axis. Our results reveal a MAT2A-mediated ferroptosis defense mechanism used by OS cells and propose a potential ferroptosis-inducing strategy for the treatment of OS patients.

Abstract Background Little is known about the access to measures of sexual and reproductive health (SRH) services among sexual minority communities in China, where sexuality-related stigma and discrimination remains high. The aim of this study is to investigate access to measures of SRH services among Chinese sexual minority youths (SMY) aged 17 to 24 years old. Methods This cross-sectional study utilizes data on 54,580 youths from the 2019–2020 National College Student Survey on Sexual and Reproductive Health, conducted across 31 provinces in mainland China. Multivariable logistic regression modelling was utilized to assess the access to SRH services among Chinese youth with different self-reported sexual orientation. Results The majority of respondents identified as heterosexual (77.6%). The remaining respondents identified as bisexual (9.0%), lesbian or gay (2.8%), others (3.02%), or unknown (7.51%). Gay men reported greater access to free contraceptives at health centers (OR 1.62, 95% CI: 1.32–1.99) and were more likely to have receive medical treatment for sexual and reproductive issues (OR 1.83, 95% CI: 1.26–2.63) compared to heterosexual men. Gay and bisexual men were also more likely to use condom at first sexual intercourse compared to heterosexual men (gay men: OR 1.38, 95% CI: 1.13–1.68; bisexual men: OR 1.33, 95% CI: 1.03–1.71). However, the associations were reversed among women (lesbians: OR 0.05, 95% CI: 0.03 to 0.08; bisexuals: 0.75, 95% CI: 0.65 to 0.86). Conclusions Although SMY reported higher utilization of SRH services compared to their heterosexual counterparts, access to SRH services remains low among Chinese youths. Greater focus should be placed on improving access to SMY-friendly SRH services among Chinese youths.

Abstract Background Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups. Methods This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified. Results A total of nine cases were included. The age range was 9–68 years (mean, 41.89 ± 19.72 years). Clinical features included virilization, amenorrhea, abdominal pain, vaginal bleeding, isosexual precocious puberty, Cushing’s syndrome, and abnormal weight gain with elevated testosterone levels. The follow up interval ranged 5–53 months and no recurrence was observed. Conclusion Ovarian steroid cell tumors covered all age groups, with manifestations of androgen excess. Younger patients appeared to have a more favorable prognosis, which provided more opportunities for these patients to pursue treatment options that will preserve reproductive function.

Abstract The widespread COVID-19 pandemic fundamentally changed many people’s ways of life. With the necessity of social distancing and lock downs across the United States, evidence shows more people engage in outdoor activities. With the utilization of location-based service (LBS) data, we seek to explore how visitation patterns to national parks changed among communities of color during the COVID-19 pandemic. Our results show that visitation rates to national parks located closer than 347 km to individuals have increased amidst the pandemic, but the converse was demonstrated amongst parks located further than 347 km from individuals. More importantly, COVID-19 has adversely impacted visitation figures amongst non-white and Native American communities, with visitation volumes declining if these communities are situated further from national parks. Our results show disproportionately low-representations amongst national park visitors from these communities of color. African American communities display a particularly concerning trend whereby their visitation to national parks is substantially lower amongst communities closer to national parks.

Abstract Purpose To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). Patients and Methods Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. Results IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (

Abstract PD-1/PD-L1 inhibitor treatments are relatively inefficacious in advanced cervical cancer patients. The presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment may be one significant barrier to efficacy. It has been shown that all-trans retinoic acid (ATRA) can differentiate MDSCs into mature myeloid cells. However, whether ATRA suppression of MDSCs function could enhance PD-L1 blockade-mediated tumor immunotherapy remains unknown. Here, the frequency of tumor-infiltrating MDSCs in cervical cancer patients was measured. ATRA was used to target MDSCs both in vitro and in tumor-bearing mice. The impact of ATRA on the human cell line HeLa was also investigated. The frequency of MDSCs and T cells was determined by flow cytometry. The expression of immunosuppressive genes was measured with quantitative real time-PCR and infiltration of immune cells was assessed by immunohistochemical examination. We found that tumor-infiltrating PD-L1+ MDSCs were more prevalent in cervical cancer patients. Blockade of PD-L1 expression in MDSCs with anti-PD-L1 antibody cannot relieve the suppressive activity of MDSCs induced by HeLa cells, while ATRA efficiently abrogated the suppressive activity of MDSCs. Furthermore, ATRA had no effect on PD-L1 expression in HeLa cells in vitro. In in vivo treatment, ATRA decreased MDSCs accumulation and increased the frequency of CD8+ T cells in BALB/C mice with U14 cervical tumors. Importantly, a combination treatment of ATRA and anti-PD-L1 antibody further delayed U14 tumor growth and increased the proportion of CD62L−CD8+ T cells, CD62L−CD4+ T cells, CD107a+CD8+ T cells as well as IFN-γ and TNF-α levels in tumors. Our results provide a rationale for the use of ATRA to suppress MDSCs and enhance anti-PD-L1 cancer immunotherapy in cervical cancer.

Trigeminal neuralgia (TN) is a severe and disabling facial pain condition and is characterized by intermittent, severe, electric shock-like pain in one (or more) trigeminal subdivisions. This pain can be triggered by an innocuous stimulus or can be spontaneous. Presently available therapies for TN include both surgical and pharmacological management; however, the lack of a known etiology for TN contributes to the unpredictable response to treatment and the variability in long-term clinical outcomes. Given this, a range of peripheral and central mechanisms underlying TN pain remain to be understood. We acquired functional magnetic resonance imaging (fMRI) data from TN patients who (1) rested comfortably in the scanner during a resting state session and (2) rated their pain levels in real time using a calibrated tracking ball-controlled scale in a pain tracking session. Following data acquisition, the data was analyzed using the conventional correlation analysis and two artificial intelligence (AI)-inspired deep learning methods: convolutional neural network (CNN) and graph convolutional neural network (GCNN). Each of the three methods yielded a set of brain regions related to the generation and perception of pain in TN. There were 6 regions that were identified by all three methods, including the superior temporal cortex, the insula, the fusiform, the precentral gyrus, the superior frontal gyrus, and the supramarginal gyrus. Additionally, 17 regions, including dorsal anterior cingulate cortex (dACC) and the thalamus, were identified by at least two of the three methods. Collectively, these 23 regions are taken to represent signature centers of TN pain and provide target areas for future studies seeking to understand the central mechanisms of TN.

BackgroundCleft lip and/or palate (CLP) can lead to severe nasolabial deformities that significantly affect the appearance of the patient. Among all types of nasolabial deformities, narrow nostril deformities are the most troublesome, causing poor and unstable surgical outcomes. The purpose of this study was to develop an algorithm for surgical method selection for revision of narrow nostril deformities secondary to CLP based on retrospective clinical data.Materials and methodsPatients with narrow nostril deformities secondary to CLP were enrolled in the study. Before surgery, patients' clinical data were collected and the width of the nasal floor and the length of the alar rim were measured. Surgical methods were determined according to the measurements. After surgery, a nostril retainer was applied for 6 months to consolidate and maintain the nostril shape. The surgical method and postsurgical changes were recorded for the final summary of the algorithm to select surgical methods for narrow nostril deformities.ResultsThe data from 9 patients were analyzed. According to the width of the nasal floor and the length of the alar rim, correct surgical methods were determined. Four patients received nasolabial skin flaps to widen the soft tissue of the nasal floor. Three patients received upper lip scar tissue flaps to treat the narrow nasal floor. For the short alar rim, free alar composite tissue flap or narrowing of the nostril of the noncleft side was recommended.ConclusionThe width of the nasal floor and the length of the alar rim are critical elements to consider when selecting the correct surgical method for revising narrow nostril deformities secondary to CLP. The proposed algorithm provides a reference for selecting surgical methods in future clinical practice.

Abstract Reticulon 3 (RTN3), an endoplasmic reticulum protein, is crucial in neurodegenerative and kidney diseases. However, the role of RTN3 in liver tissues has not been described. Here, we employed public datasets, patients, and several animal models to explore the role of RTN3 in nonalcoholic fatty liver disease (NAFLD). The underlying mechanisms were studied in primary hepatocytes and L02 cells in vitro. We found an increased expression of RTN3 in NAFLD patients, high‐fat diet mice, and oxidized low‐density lipoprotein‐treated L02 cells. The RTN3 transgenic mice exhibited the phenotypes of fatty liver and lipid accumulation. Single‐cell RNA sequencing analysis indicated that increased RTN3 might induce mitochondrial dysfunction. We further showed this in primary hepatocytes, the L02 cell line, and the Caenorhabditis elegans strain. Mechanistically, RTN3 regulated these events through its interactions with glucose‐regulated protein 78 (GRP78), which further inhibited the adenosine 5 monophosphate‐activated protein kinase (AMPK)–isocitrate dehydrogenase 2 (IDH2) pathway. In the end, knockout of RTN3 relieved fatty liver and mitochondrial dysfunction. Our study indicated that RTN3 was important in NAFLD and lipid catabolism and that an increase in RTN3 in the liver might be a risk factor for nonalcoholic steatohepatitis and NAFLD.

Purpose: Brain metastases are a common development in patients with malignant solid tumors. Stereotactic radiosurgery (SRS) has a long track record of effectively and safely treating these patients, with some limitations to the use of single fraction SRS based on size and volume. In this study, we reviewed outcomes of patients treated using SRS and fractionated SRS (fSRS) to compare predictors and outcomes of those treatments. Methods and Materials: Two hundred patients treated with SRS or fSRS for intact brain metastases were included. We tabulated baseline characteristics and performed a logistic regression to identify predictors of fSRS. Cox regression was used to identify predictors of survival. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. A receiver operating characteristic curve was generated to determine timepoint from planning to treatment associated with local failure. Results: The only predictor of fSRS was tumor volume >2.061 cm3. There was no difference in local failure, toxicity, or survival by fractionation of biologically effective dose. Predictors of worse survival were age, extracranial disease, history of whole brain radiation therapy, and volume. Receiver operating characteristic analysis identified 10 days as potential factor in local failure. At 1 year, local control was 96.48 and 76.92% for those patients treated before or after that interval, respectively (P = .0005). Conclusions: Fractionated SRS is a safe and effective alternative for patients with larger volume tumors not suitable for single fraction SRS. Care should be taken to treat these patients expeditiously as a delay was shown to affect local control in this study.

Gay, bisexual and other men who have sex with men (GBMSM) college students in China have unique sexual health challenges, including a higher risk of HIV infection, stigma and discrimination against LGBTQ (lesbian, gay, bisexual, transgender, and queer) population, and limited access to LGBTQ-affirmative sexual health support. Nonetheless, previous research or policymaking has rarely addressed the students' needs for sexual health support from their perspectives. This study aims to explore GBMSM college students' perceptions and attitudes to current sexual health resources, the challenges they encounter, and their expectations to acquiring LGBTQ-affirmative sexual health information and services. The exploration was carried out through field visits and in-depth interviews with 26 GBMSM college students and eight relevant stakeholders in five cities in China. Qualitative thematic analysis was applied to the interview transcripts and fieldwork memos. Four themes emerged around the preference and needs of GBMSM students in dealing with their sexual health challenges: the association between tackling sexual health challenges and entering LGBTQ communities, the roles of emotional attachment in shaping the preference for HIV-related care and support, the desired modes of acquiring sexual health support, and the current unmet service needs. We discovered that the information-and-care-seeking behaviors of GBMSM college students are highly influenced by and connected to their participation in online and in-person LGBTQ communities. Due to the overall stigmatizing sociocultural environment of LGBTQ in China, GBMSM college students tend to rely on LGBTQ communities, seeking trust and a sense of belongingness for tackling their sexual health challenges. Conventional school-based sexual health educational programs, which often apply top-down, stigma-and-fear-based, and non-LGBTQ-inclusive teaching strategies, rarely help GBMSM college students to solve sexual health problems in real life. GBMSM college students are eager to have LGBTQ-affirmative "health managers" who can understand their emotional experiences and interpersonal contexts and assist them with sexual health issues. However, such support is generally perceived as limited by the students. Our study highlights these unmet needs of the GBMSM students and emphasizes the importance of developing future LGBTQ-affirmative sexual health programs among Chinese GBMSM college students and young GBMSM in general.

The majority of autoimmune diseases affect more women than men, suggesting an important role for sex hormones in regulating immune response. Current research supports this idea, highlighting the importance of sex hormones in both immune and metabolic regulation. Puberty is characterized by drastic changes in sex hormone levels and metabolism. These pubertal changes may be what forms the gulf between men and women in sex bias towards autoimmunity. In this review, a current perspective on pubertal immunometabolic changes and their impact on the pathogenesis of a select group of autoimmune diseases is presented. SLE, RA, JIA, SS, and ATD were focused on in this review for their notable sex bias and prevalence. Due to both the scarcity of pubertal autoimmune data and the differences in mechanism or age-of-onset in juvenile analogues often beginning prior to pubertal changes, data on the connection between the specific adult autoimmune diseases and puberty often relies on sex hormone influence in pathogenesis and established sex differences in immunity that begin during puberty.

ABSTRACT This study analyzed the epidemiological characteristics of 3,464 human plague cases and the distribution pattern of 4,968 Yersinia pestis isolates from humans, hosts, and vector insects from 1950 to 2020 among two natural plague foci in Yunnan Province, China. These foci include the Rattus flavipectus plague focus of the Yunnan, Guangdong, and Fujian provinces and the Apodemus chevrieri-Eothenomys miletus plague focus of the highlands of northwestern Yunnan Province. The case fatality rate for plague in humans was 18.39% (637/3,464), and the total isolation rate of Y. pestis was 0.17% (4,968/2,975,288). Despite that the frequency of human cases declined rapidly, the animal plague fluctuated greatly, alternating between activity and inactivity in these foci. The tendency among human cases can be divided into 4 stages, 1950 to 1955, 1956 to 1989, 1990 to 2005, and 2006 to 2020. Bubonic plague accounted for the majority of cases in Yunnan, where pneumonic and septicemic plague rarely occurred. The natural plague foci have been in a relatively active state due to the stability of local ecology. Dense human population and frequent contact with host animals contribute to the high risk of human infection. This study systematically analyzed the epidemic pattern of human plague and the distribution characteristics of Y. pestis in the natural plague foci in Yunnan, providing a scientific basis for further development and adjustment of plague prevention and control strategies. IMPORTANCE Yunnan is the origin of the third plague pandemic. The analysis of human and animal plague characteristics of plague foci in Yunnan enlightens the prevention and control of the next plague pandemics. The plague characteristics of Yunnan show that human plague occurred when animal plague reached a certain scale, and strengthened surveillance of animal plague and reducing the density of host animals and transmission vectors contribute to the prevention and control of human plague outbreaks. The phenomenon of alternation between the resting period and active period of plague foci in Yunnan further proves the endogenous preservation mechanism of plague.

Abstract Underwater exploration has been an attractive topic for understanding the very nature of the lakes and even deep oceans. In recent years, extensive efforts have been devoted to developing functional materials and their integrated devices for underwater information capturing. However, there still remains a great challenge for water depth detection and vibration monitoring in a high-efficient, controllable, and scalable way. Inspired by the lateral line of fish that can sensitively sense the water depth and environmental stimuli, an ultrathin, elastic, and adaptive underwater sensor based on Ecoflex matrix with embedded assembled graphene sheets is fabricated. The graphene structured thin film is endowed with favourable adaptive and morphable features, which can conformally adhere to the structural surface and transform to a bulged state driven by water pressure. Owing to the introduction of the graphene-based layer, the integrated sensing system can actively detect the water depth with a wide range of 0.3–1.8 m. Furthermore, similar to the fish, the mechanical stimuli from land (e.g. knocking, stomping) and water (e.g. wind blowing, raining, fishing) can also be sensitively captured in real time. This graphene structured thin-film system is expected to demonstrate significant potentials in underwater monitoring, communication, and risk avoidance.

The convolution operation is the most critical component in recent surge of deep learning research. Conventional 2D convolution needs O(C2K2) parameters to represent, where C is the channel size and K is the kernel size. The amount of parameters has become really costly considering that these parameters increased tremendously recently to meet the needs of demanding applications. Among various implementations of the convolution, separable convolution has been proven to be more efficient in reducing the model size. For example, depth separable convolution reduces the complexity to O(C⋅(C+K2)) while spatial separable convolution reduces the complexity to O(C2K). However, these are considered ad hoc designs which cannot ensure that they can in general achieve optimal separation. In this research, we propose a novel and principled operator called optimized separable convolution by optimal design for the internal number of groups and kernel sizes for general separable convolutions can achieve the complexity of O(C32K). When the restriction in the number of separated convolutions can be lifted, an even lower complexity at O(C⋅log(CK2)) can be achieved. Experimental results demonstrate that the proposed optimized separable convolution is able to achieve an improved performance in terms of accuracy-#Params trade-offs over both conventional, depth-wise, and depth/spatial separable convolutions.

Highlights An elastic, superhydrophobic and conductive thin film inspired by the natural self-supported superhydrophobic butterfly wings enabled by a controllable composite of assembled carbon nanotube and elastomer is fabricated. Through the adjustment of hydrophobic elastomeric coating, the surface wettability can be effectively controlled and still maintain superhydrophobic characteristics under the applied strain of 60%. The achieved film can function as a self-supported smart umbrella to sensitively monitor the day weather and perform water rescue Abstract Two-dimensional (2D) soft materials, especially in their self-supported forms, demonstrate attractive properties to realize biomimetic morphing and ultrasensitive sensing. Although extensive efforts on design of self-supported functional membranes and integrated systems have been devoted, there still remains an unexplored regime of the combination of mechanical, electrical and surface wetting properties for specific functions. Here, we report a self-supported film featured with elastic, thin, conductive and superhydrophobic characteristics. Through a well-defined surface modification strategy, the surface wettability and mechanical sensing can be effectively balanced. The resulted film can function as a smart umbrella to achieve real-time simulated raining with diverse frequencies and intensity. In addition, the integrated umbrella can even response sensitively to the sunlight and demonstrate a positively correlation of current signals with the intensity of sun illumination. Moreover, the superhydrophobic umbrella can be further employed to realize water rescue, which can take the underwater object onto water surface, load and rapidly transport the considerable weight. More importantly, the whole process of loaded objects and water flow velocity can be precisely detected. The self-supported smart umbrella can effectively monitor the weather and realize a smart water rescue, demonstrating significant potentials in multifunctional sensing and directional actuation in the presence of water.

The phenotypic characteristics of soybean leaves are of great significance for studying the growth status, physiological traits, and response to the environment of soybeans. The segmentation model for soybean leaves plays a crucial role in morphological analysis. However, current baseline segmentation models are unable to accurately segment leaves in soybean leaf images due to issues like leaf overlap. In this paper, we propose a target leaf segmentation model based on leaf localization and guided segmentation. The segmentation model adopts a two-stage segmentation framework. The first stage involves leaf detection and target leaf localization. Based on the idea that a target leaf is close to the center of the image and has a relatively large area, we propose a target leaf localization algorithm. We also design an experimental scheme to provide optimal localization parameters to ensure precise target leaf localization. The second stage utilizes the target leaf localization information obtained from the first stage to guide the segmentation of the target leaf. To reduce the dependency of the segmentation results on the localization information, we propose a solution called guidance offset strategy to improve segmentation accuracy. We design multiple guided model experiments and select the one with the highest segmentation accuracy. Experimental results demonstrate that the proposed model exhibits strong segmentation capabilities, with the highest average precision (AP) and average recall (AR) reaching 0.976 and 0.981, respectively. We also compare our segmentation results with current baseline segmentation models, and multiple quantitative indicators and qualitative analysis indicate that our segmentation results are better.

Accurate detection and counting of live pigs are integral to scientific breeding and production in intelligent agriculture. However, existing pig counting methods are challenged by heavy occlusion and varying illumination conditions. To overcome these challenges, we proposed IO-YOLOv5 (Illumination-Occlusion YOLOv5), an improved network that expands on the YOLOv5 framework with three key contributions. Firstly, we introduced the Simple Attention Receptive Field Block (SARFB) module to expand the receptive field and give greater weight to important features at different levels. The Ghost Spatial Pyramid Pooling Fast Cross Stage Partial Connections (GSPPFC) module was also introduced to enhance model feature reuse and information flow. Secondly, we optimized the loss function by using Varifocal Loss to improve the model’s learning ability on high-quality and challenging samples. Thirdly, we proposed a public dataset consisting of 1270 images and 15,672 pig labels. Experiments demonstrated that IO-YOLOv5 achieved a mean average precision (mAP) of 90.8% and a precision of 86.4%, surpassing the baseline model by 2.2% and 3.7% respectively. By using a model ensemble and test time augmentation, we further improved the mAP to 92.6%, which is a 4% improvement over the baseline model. Extensive experiments showed that IO-YOLOv5 exhibits excellent performance in pig recognition, particularly under heavy occlusion and various illuminations. These results provide a strong foundation for pig recognition in complex breeding environments.

Background: The adult stage is an important period in the life cycle of Angiostrongylus cantonensis, as it is at this stage that male and female worms produce thousands of fertilized eggs daily. Methods: To explore the transcriptional details of adult male and female A. cantonensis, three groups of male and female adult worms were collected, and their transcriptome profiles were analyzed using an Illumina next-generation sequencing platform. A total of 283,910,174 clean reads were obtained, and 137,626 unigenes and 237,059 transcripts were then generated. Unigenes were successfully annotated by querying the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), NCBI non-redundant protein sequences (NR), PFAM, STRING, and SWISS-PROT databases. Then, differentially expressed genes (DEGs) between the 2 genders were identified. The GO and KEGG databases were used for DEG annotation, and a number of DEG annotations were enriched. Results: The results obtained from querying DEGs using the GO and KEGG databases revealed that male and female adult worms exhibited differences in metabolism and production. Protein phosphorylation, ion transport, and calcium transport were all significantly enriched according to GO annotation. A number of other pathways were also enriched according to KEGG enrichment annotation, including the pentose phosphate pathway, nitrogen metabolism, oocyte meiosis pathway, neuroactive ligand-receptor interaction, calcium signaling pathway, transforming growth factor β (TGF-β) signaling pathway etc. Conclusion: We hypothesized that the nervous system of the worm plays a key role in the physiological regulation of adult A. cantonensis, and based on this, the function of the calcium-signaling pathway should be investigated.

Background: Phenylephrine is the first-line drug used to maintain blood pressure in cesarean delivery. However, it poses a high risk of bradycardia and depression of cardiac activity in pregnant women. Consequently, norepinephrine has gained popularity over the recent years, as an alternative to Phenylephrine because it is thought that prophylactic use of vasopressors may reduce the incidence of hypotension after spinal anesthesia. This systematic review compared the efficacy of both treatments.Methods: We searched the following databases; CNKI, PubMed, Embase, Web of science, clinicaltrials.gov, Medline and Cochrane Library, for randomized controlled trials comparing the prophylactic efficacy of norepinephrine and phenylephrine on elective cesarean delivery under spinal anesthesia. The search period was from inception to July 2022, and the primary outcome indicator was incidence of bradycardia. Statistical analysis was conducted on Rev manager 5.4, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to evaluate the quality of evidence from each main finding.Results: A total of 12 papers were included in the analysis. The incidence of bradycardia (RR = 0.37, 95% CI: 0.28 to 0.49, p < 0.00001) and reactive hypertension (RR = 0.58, 95% CI 0.40 to 0.83, p = 0.003) was significantly lower in the norepinephrine (NE) group compared with the phenylephrine (PE) category. In contrast, there were no statistical differences in the umbilical cord blood gas analysis pH values between the groups (arterial: MD = 0.00, 95% CI −0.00 to 0.01, p = 0.22, vein: MD = 0.01, 95% CI −0.00 to 0.02, p = 0.06). The incidence of hypotension, nausea, and vomiting did not differ significantly between the NE and PE groups (hypotension: 23% vs. 18%; nausea: 14% vs. 18%; vomiting: 5% vs. 7%, respectively).Conclusion: Prophylactic use of norepinephrine is safe and effective in maintaining maternal hemodynamics without causing adverse events to either the pregnant woman or fetus.Systematic Review Registration: website https://www.crd.york.ac.uk/prospero/, identifier CRD42022347095