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Surface sediment samples were collected from the surrounding waters of the two largest tourist islands in Sanya, China, to compare and evaluate the sources, distribution, and ecological risks of 21 organochlorine pesticides (OCPs). The total concentration of OCPs ranged from 1.35 to 5.0 ng/g. Among the OCPs, ΣDDTs accounted for the largest proportion, followed by ΣHCHs. The concentrations of HCHs and DDTs from the west side of West Island were significantly higher than those from the east side, and fine-grained sediments exhibited a stronger adsorption effect on OCPs. Source analysis indicated that the area experienced new inputs of HCH pollutants, while historical residues of HCHs remained high. Residual OCPs are still widely present in the environment, transported mainly by river runoff, with a smaller portion originating from atmospheric deposition and ship paints. Ecological risk assessment results showed that factors occasionally causing adverse biological effects include Heptachlor epoxide, 4,4'-DDE, ΣDDT, Dieldrin, Endrin, and γ-HCH, while other factors rarely caused negative biological effects. Potential ecological effect evaluations indicated that stations SY03, SY04, SY06, and SY09 were classified as having moderate ecological effect levels, while other stations were classified as having no ecological effects. Strengthened investigation, monitoring, and control of pollutant sources in ecologically impacted areas are necessary. This study fills a data gap for the region and provides an academic foundation for environmental protection and the sustainable development of tourism resources.

BackgroundThe clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear.MethodRetrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed.ResultsThe results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006).ConclusionsCompared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

It has become a consensus that large-scale hydraulic fracturing is adopted to achieve the stimulation of unconventional oil and gas reservoir. The complex fracture network formed by fracturing is closely related to the effect of reservoir stimulation, which has extremely complicated evolution process. Therefore, it is necessary to study the evolution law of fracture network in large-scale hydraulic fracturing of unconventional reservoirs. In this article, the geological engineering parameters of horizontal well H in shale gas reservoir in southern Sichuan are taken as an example, a three-dimensional fracture network expansion model is established based on the boundary element method and finite volume method, and the simulation of the complex fracture network in a whole well section is carried out to analyze the evolution law of reservoir fracture network under different geological and engineering parameters. The results show that the horizontal stress field distribution has a significant effect on fracture geometric form. Hydraulic fractures in reservoirs with larger horizontal stress difference have stronger directivity, while the horizontal wellbore tends to obtain better reservoir stimulation results when it is parallel to the minimum horizontal principal stress setting. The conjugated natural fracture developed in the reservoir inhibits the hydraulic expansion fractures in both directions. Although it increases the complexity of the fractures, it is not necessarily conducive to improving the reservoir stimulation effectiveness. The lower the strength of natural fracture is, the more complex the fracture geometric form becomes, and the smaller the stimulated reservoir volume is. Correspondingly, the higher the strength of natural fracture is, the simpler the fracture geometric form becomes, and the larger the stimulated reservoir volume is. Suitable fracturing construction displacement can not only contribute to form a more complex fracture distribution, but also help to obtain a larger stimulated reservoir volume. The optimal construction displacement ranges from 10 to 14 m3/min. Low viscosity fracturing fluids are suitable for the formation of long-narrow fractures and able to connect with the remote reservoir and form complex fracture networks. Lower viscosity fluids can be used to achieve better reservoir stimulation effectiveness when sand-carrying capacity is met.

Swertia mussotii is the most authentic raw material used in Tibetan medicine in China for its various bioactivities. This natural medicine resource is at risk of being exhausted due to the double interference of climate change and anthropogenic over-collection. Little is known about habitat characteristics and the crucial environmental factors that influence the levels of active ingredients. The goal of this study is to understand the variability in the bioactive compound content of a wide range of wild S. mussotii as it adapts to changing environmental conditions. The target compound content of the whole plant material was analyzed with the environmental explanatory variables of the field sample sites using a constrained ordination method for their correlation analysis. The results show that 16.3 percent of the sampled wild S. mussotii populations with the highest bioactive content can be grouped into the elite type. The most prominent environmental variables affecting the content of major bioactive products include altitude, aspect, soil TK content, Fe content, and C/N and N/P ratios. Altitude and aspect put indirect effects that are mediated by plant height and density, N/P ratio puts a direct effect, while soil TK content, Fe content and C/N ratio have both direct and indirect effects on the bioactivity of S. mussotii. In addition to the total negative effects of altitude and C/N ratio, the remaining factors play a driving role. These findings demonstrate variation by geographical conditions across S. mussotii accessions for physiologic responses and secondary compounds in wild populations. The knowledge gained from this study can be used for environmental and plant physiology research, efficient collection of naturally active compounds, and conservation strategies for rare natural plant resources.

Toon buds, a popular woody vegetable, contain large amounts of nutrients. However, toon buds have strong respiratory metabolism after harvest and are highly prone to decay, resulting in quality deterioration. Low temperature can effectively inhibit postharvest senescence of toon buds. GC-TOF-MS combined with quantitative real-time PCR was used to elucidate the toon bud deterioration mechanism after harvest by analyzing the difference in the relative contents of primary metabolites and their derivatives, and the expression of key genes associated with metabolic pathways in toon buds between low temperature and room temperature storages for 72 h. Results showed that the ethylene synthesis in toon buds accelerated under room temperature storage, along with significant changes in the primary metabolic pathway. The catabolism of amino acids, fatty acids, and cell membrane phospholipids was accelerated, and the gluconeogenesis synthesis was strengthened. Moreover, the sucrose synthesis was increased, the glycolysis and TCA cycle were broken down, and the pentose phosphate pathway was vigorous. As metabolic intermediates, organic acids were considerably accumulated. Moreover, varieties of toxic compounds were produced in parallel with the activation of aromatic compounds. This work provided a comprehensive understanding of the metabolic regulation, thereby revealing how low and room temperatures differentially influenced the quality deterioration of postharvest toon buds.

Simple summarySomatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies.BackgroundHomologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients.MethodsWe performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes.ResultsTP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset

BackgroundIndocyanine green (ICG) is a nontoxic, albumin-bound, liver-metabolized fluorescent iodide dye that has been widely utilized in clinical applications since the mid-1950s. However, after the 1970s, in-depth research on the fluorescence properties of ICG greatly expanded its application in the medical field.MethodsIn our mini-review, we searched the relevant literature on common oncology surgeries from PubMed, including lung cancer, breast cancer, gastric cancer, colorectal cancer, liver cancer, and pituitary tumors, using keywords such as indocyanine green, fluorescence imaging technology, and near-infrared fluorescence imaging. In addition, the application of targeted ICG photothermal technology in tumor therapy is briefly mentioned.ResultsIn this mini-review, we analyzed studies on ICG fluorescence imaging in common surgical oncology and offered a thorough analysis of each form of cancer or tumor.ConclusionICG has demonstrated significant potential in the detection and treatment of tumors in current clinical practice, although many applications are still in the preliminary stages, and multicenter studies are still required to more precisely define its indications, effectiveness, and safety.

BackgroundWe aimed to compare the detection rates of prostate cancer (PCa) and clinically significant prostate cancer(csPCa) by biparametric (bp-) and multiparameter magnetic resonance imaging (mpMRI).Materials and MethodsA total of 699 patients who underwent transperineal prostate biopsy in the Department of Urology, the Second Affiliated Hospital of Nantong University from January 2018 to December 2021 were retrospectively reviewed. Multivariate analysis was used to explore the influencing factors associated with the detection rates of PCa and csPCa. According to MRI examination before biopsy, the patients were divided into bpMRI group and mpMRI group. The detection rates of PCa and csPCa by bpMRI and mpMRI were compared. Furthermore, stratified analysis was performed for patients in these two groups to compare the detection rates of PCa and csPCa at different tPSA intervals, different prostate volume (PV) intervals and different PI-RADS V2 scores.ResultsA total of 571 patients were finally analyzed in this study after exclusion, and the overall detection rate of PCa was 54.5%. Multivariate analysis showed that patient age, tPSA level, prostate volume and PI-RADS V2 score were independent risk factors affecting the detection rates of PCa and csPCa. The detection rates of PCa and csPCa by bpMRI and mpMRI were comparable (51.3% vs. 57.9%, 44.0% vs. 48.0%, both P > 0.05), with no statistical significance. In the tPSA 10–20 ng/ml interval, the detection rates of PCa (59.72% vs. 40.35%, P = 0.011) and csPCa (51.39% vs. 28.82%, P = 0.005) by mpMRI were significantly higher than those by bpMRI, while in other tPSA interval (tPSA 60 ml) and different PI-RADS V2 scores (3, 4, and 5), the detection rates of PCa and csPCa were comparable between the two groups.ConclusionFor detecting PCa and csPCa, bpMRI and mpMRI had similar diagnostic efficacies, whereas mpMRI detected more PCa and csPCa in the tPSA interval of 10–20 ng/ml.

BackgroundProgrammed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC.MethodsWe retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared.ResultsA total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P

Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs).Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied.Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group.Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.

Casing deformation (CD) will seriously affect the fracturing progress and stimulation effect of shale gas. Taking 105 gas wells in the Luzhou shale gas area in southern Sichuan as an example, the CD prediction model was established by introducing the fracture operation curve diagnosis method to analyze the changes in net pressure and propagation mode during fracturing. The fracturing stage induced by CD is called the excited (ET) stage, and the fracturing stage that occurs during CD is called the CD stage. It is concluded that the change of net pressure and the propagation mode are coupled with each other. By natural fracture development, formation curvature and horizontal well trajectory, natural fractures and bedding have been active by high fracturing strength, or because of the frequent crossing-layer in single stage, local stress reverse, makes the net pressure decrease and makes the formation in strike-slip stress state to reverse fault stress state, liquid leak-off and blocked fracture propagation time are increased, thus inducing CD. According to the response law induced by CD, the CD pre-control mode is formed, and the CD pre-control technology is established to quantitatively evaluate the wellbore risk and optimize the fracturing operation order and time arrangement. The CD rate is reduced from 56% in the early stage to 20%, and the integrity of the wellbore is guaranteed to be 100%. The method has strong applicability in the field and can be further popularized.

BackgroundThe purpose of this study is to predict overall survival (OS) and lung cancer-specific survival (LCSS) in patients with stage IIIA-N2 unresectable lung squamous cell cancer (LUSC), lung adenocarcinoma (LUAD), and large cell neuroendocrine cancer (LCNEC) by constructing nomograms and to compare risk and prognostic factors affecting survival outcomes in different histological subtypes.MethodsWe included 11,505 unresectable NSCLC patients at stage IIIA-N2 between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Moreover, competition models and nomograms were developed to predict prognostic factors for OS and LCSS.ResultsAnalysis of the SEER database identified 11,505 NSCLC patients, of whom 5,559 (48.3%) have LUAD, 5,842 (50.8%) have LUSC, and 104 (0.9%) have LCNEC. Overall, both OS and LCSS were significantly better in stage IIIA-N2 unresectable LUAD than in LCNEC, while there was no statistically significant difference between LUSC and LCNEC. Age, gender, T stage, chemotherapy, and radiotherapy were significantly associated with OS rates in LUAD and LUSC. However, chemotherapy was the only independent factor for LCNEC (p < 0.01).From competitive risk models, we found that older age, larger tumors, non-chemotherapy and non-radiotherapy were associated with a increased risk of death from LUAD and LUSC. Unlike prognostic factors for OS, our study showed that both chemotherapy and radiotherapy were all LCNEC-specific survival factors for both LCSS and non-LCSS LCNEC.ConclusionOur study reports that unresectable patients with stage IIIA-N2 LCNEC and LUSC have worse LCSS than LUAD. The study’s first prognostic nomogram constructed for patients with unresectable stage IIIA-N2 NSCLC can accurately predict the survival of different histological types, which may provide a practical tool to help clinicians assess prognosis and stratify these prognostic risks to determine which patients should be given an optimized individual treatment strategy based on histology.

IntroductionCoronary artery aneurysm (CAA) is a localized coronary artery dilatation that exceeds 1. 5 times the diameter of a standard adjacent segment or the largest coronary vessel. When the expansion is > 2 cm, it is called a “giant” coronary artery aneurysm. Giant coronary artery aneurysm rupture is extremely rare and fatal.Case presentationWe present a rare case of a 27 years old male with a giant coronary artery aneurysm rupture, but no catastrophic events occurred immediately. He was initially misdiagnosed as having a mediastinal mass with CT (computed tomography). The cardiac ultrasound showed no pericardial effusion. But The cardiac CTA (computed tomography angiography) showed a giant coronary aneurysm rupture with hematoma formation. He eventually underwent surgery and was followed up for 2 months without complications.ConclusionWe report this case of a ruptured giant coronary aneurysm because of its infrequent occurrence in coronary artery disease. It is tough to distinguish this disease from a mediastinal tumor, and chest MRI and cardiac CTA are crucial tests. Finally, surgical resection may be the right choice for coronary aneurysm rupture. More cases need to be reported to facilitate the preoperative diagnosis of this rare coronary aneurysm.

BackgroundCombined small cell lung carcinoma is defined as cancer tissues that mainly contain small cell lung cancer (SCLC) components with non-SCLC (NSCLC) histopathological types. The most common part of NSCLC is squamous cell carcinoma or large cell carcinoma. Combined SCLC (CSCLC) contains adenocarcinoma is extremely rare.Case PresentationWe reported a case with surgically treated diagnosed as CSCLC with adenocarcinoma in an elderly and we summarized the clinical features of this disease. The patient has remained well for over 2 weeks after the treatment.ConclusionThere are still few research reports on CSCLC. Since the survival time of patients with advanced CSCLC is shorter than that of simple SCLC, the recommended treatment for CSCLC is early detection and early surgery. In order to facilitate preoperative diagnosis and avoid misdiagnosis of such rare diseases, more cases need to be reported.

Background: Surgical treatment is usually suitable for patients with esophageal leiomyoma. Video-assisted thoracic surgery (VATS) offers a minimally invasive approach to thoracotomy. However, there is no clear conclusion on whether VATS can achieve an equal or even better surgical effect when compared with the traditional open approach in the treatment of esophageal leiomyoma. We performed this meta-analysis to explore and compare the outcomes of VATS vs. thoracotomy for patients with esophageal leiomyoma.Methods: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases were searched for full-text literature citations. The quality of the articles was evaluated using the Newcastle–Ottawa Scale and the data were analyzed using the Review Manager 5.3 software. Fixed or random effect models were applied according to heterogeneity.Results: A total of 8 studies with 290 patients, of whom 141 patients were in the VATS group and 149 in the thoracotomy group, were involved in the analysis. Compared with thoracotomy, VATS was associated with shorter operative time, less blood loss in operation, and shorter postoperative hospital stay. There is no significant difference in postoperative pleural drainage day and postoperative complications between the two groups.Conclusions: VATS has more advantages over thoracotomy, indicating that VATS is better than thoracotomy in terms of postoperative recovery. We look forward to more large-sample, high-quality studies published in the future.

Background: A pink color change occasionally found by us under magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and was designated the “pink pattern”. The purposes of this study were to determine the relationship between the pink pattern and the cytopathological changes in gastric cancer cells and whether the pink pattern is useful for the diagnosis of EGC.Methods: The color features of ME-NBI images and pathological images of cancerous gastric mucosal surfaces were extracted and quantified. The cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-cytoplasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficacy of the pink pattern for EGC. The diagnostic values, such as the area under the curve (AUC), the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of test 1 and test 2 were compared.Results: The cosine similarity between the color values of ME-NBI images and pathological images of 20 lesions was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV, and NPV of test 2 were significantly better than those of test 1 for all endoscopists and for the junior and experienced groups.Conclusions: The pink pattern observed in ME-NBI images correlated strongly with the change in the nucleus-to-cytoplasm ratio of gastric epithelial cells, and could be considered a useful marker for the diagnosis of differentiated EGC.

Background and Objective: This study was undertaken to evaluate how safe and viable the use of video-assisted thoracoscopic day surgery (VATDS) is for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC).Methods: Data obtained from the selected patients with NSCLC who underwent video-assisted thoracoscopic surgery (VATS) in the same medical group were analyzed and a single-center, propensity-matched cohort study was performed. In total, 353 individuals were included after propensity score matching (PSM) with 136 individuals in the day surgery group (DSG) and 217 individuals in the inpatient surgery group (ISG).Results: The 24-h discharge rate in the DSG was 93.38% (127/136). With respect to the postoperative complications (PPCs), no difference between the two groups was found (DSG vs. ISG: 11.76 vs. 11.52%, p = 0.933). In the DSG, a shorter length of stay (LOS) after surgery (1.47 ± 1.09 vs. 2.72 ± 1.28 days, p < 0.001) and reduced drainage time (8.45 ± 3.35 vs. 24.11 ± 5.23 h, p < 0.001) were found, while the drainage volume per hour (mL/h) was not notably divergent between the relevant groups (p = 0.312). No difference was observed in the cost of equipment and materials between the two groups (p = 0.333). However, the average hospital cost and drug cost of the DSG were significantly lower than those of the ISG (p < 0.001).Conclusion: The study indicated that the implementation of VATDS showed no difference in PPCs, but resulted in shorter in-hospital stays, shorter drainage times, and lower hospital costs than inpatient surgery. These results indicate the safety and feasibility of VATDS for a group of highly selected patients with early-stage NSCLC.

Based on logging, seismic, fracturing and production data from 301 productive wells in Longmaxi Formation in Changning shale gas field of southern Sichuan basin, the various influence factors of shale gas stimulated potential have been analyzed to carry out the correlation study with estimated ultimate recovery (EUR) of the same fracturing operation intensity to fully clarify the main controlling factors for shale gas stimulated potential. The results show that matrix brittleness, fracture propagation and reservoir properties are the 3 key secondary potentials that control shale gas stimulation potential. The matrix brittleness is controlled by elastic modulus, Poisson’s ratio, Type I and II fracture toughness, which reflects the uniformity of hydraulic fracture propagation. Fracture propagation is controlled by critical net pressure, which reflects the scale of hydraulic fracture propagation. Reservoir properties are controlled by porosity, total organic carbon content (TOC) and horizontal interval differences, which reflect the enrichment conditions and dynamic production capacity of reservoir resources. The matrix brittleness index, fracture propagation index, reservoir properties index and their combined stimulated potential index were formed by using the above 7 parameters to verify and apply the wells in Changning shale gas field. Results show that the matrix brittleness index and length-width ratio of hydraulic fracture was significantly negative correlation, the fracture propagation index and stimulated reservoir volume (SRV) were significantly positive correlation, stimulated potential index was developed taking into account enrichment & exploitation potential. In areas where the value is greater than 0.5, increasing the fracturing scale can effectively improve the well productivity; in areas less than 0.5, increasing the fracturing scale has an upper limit on the increase of productivity, so the physical properties of the reservoir itself play a significant role in controlling the production of shale gas wells.

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 vs 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2–0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31–0.96; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18–1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.

Predicting protein-ligand interactions using artificial intelligence (AI) models has attracted great interest in recent years. However, data-driven AI models unequivocally suffer from a lack of sufficiently large and unbiased datasets. Here, we systematically investigated the data biases on the PDBbind and DUD-E datasets. We examined the model performance of atomic convolutional neural network (ACNN) on the PDBbind core set and achieved a Pearson R2 of 0.73 between experimental and predicted binding affinities. Strikingly, the ACNN models did not require learning the essential protein-ligand interactions in complex structures and achieved similar performance even on datasets containing only ligand structures or only protein structures, while data splitting based on similarity clustering (protein sequence or ligand scaffold) significantly reduced the model performance. We also identified the property and topology biases in the DUD-E dataset which led to the artificially increased enrichment performance of virtual screening. The property bias in DUD-E was reduced by enforcing the more stringent ligand property matching rules, while the topology bias still exists due to the use of molecular fingerprint similarity as a decoy selection criterion. Therefore, we believe that sufficiently large and unbiased datasets are desirable for training robust AI models to accurately predict protein-ligand interactions.

The SCN5A gene encodes the alpha subunit of the main cardiac sodium channel Nav1.5. This channel predominates inward sodium current (INa) and plays a critical role in regulation of cardiac electrophysiological function. Since 1995, SCN5A variants have been found to be causatively associated with Brugada syndrome, long QT syndrome, cardiac conduction system dysfunction, dilated cardiomyopathy, etc. Previous genetic, electrophysiological, and molecular studies have identified the arrhythmic and cardiac structural characteristics induced by SCN5A variants. However, due to the variation of disease manifestations and genetic background, impact of environmental factors, as well as the presence of mixed phenotypes, the detailed and individualized physiological mechanisms in various SCN5A-related syndromes are not fully elucidated. This review summarizes the current knowledge of SCN5A genetic variations in different SCN5A-related cardiac disorders and the newly developed therapy strategies potentially useful to prevent and treat these disorders in clinical setting.

Winds in the nighttime upper thermosphere are often observed to mimic the ionospheric plasma convection at polar latitudes, and whether the same is true for the daytime winds remains unclear. The dayside sector is subject to large temperature gradient set up by solar irradiance and it also contains the cusp, which is a hotspot of Poynting flux and a region with the strongest soft particle precipitation. We examine daytime winds using a Scanning Doppler Imager (SDI) located at the South Pole, and investigate their distribution under steadily positive and negative IMF By conditions. The results show that daytime winds exhibit significant differences from the plasma convection. Under negative IMF By conditions, winds flow in the same direction as the plasma zonally, but have a meridional component that is strongest in the auroral zone. As a result, winds are more poleward-directed than the plasma convection within the auroral zone, and more westward-directed in the polar cap. Under positive IMF By conditions, winds can flow zonally against the plasma in certain regions. For instance, they flow westward in the polar cap despite the eastward plasma convection there, forming a large angle relative to the plasma convection. The results indicate that ion drag may not be the most dominant force for daytime winds. Although the importance of various forcing terms cannot be resolved with the utilized dataset, we speculate that the pressure gradient force in the presence of cusp heating serves as one important contributor.

Plants are often subjected to various environmental stresses during their life cycle, among which drought stress is perhaps the most significant abiotic stress limiting plant growth and development. Arbuscular mycorrhizal (AM) fungi, a group of beneficial soil fungi, can enhance the adaptability and tolerance of their host plants to drought stress after infecting plant roots and establishing a symbiotic association with their host plant. Therefore, AM fungi represent an eco-friendly strategy in sustainable agricultural systems. There is still a need, however, to better understand the complex mechanisms underlying AM fungi-mediated enhancement of plant drought tolerance to ensure their effective use. AM fungi establish well-developed, extraradical hyphae on root surfaces, and function in water absorption and the uptake and transfer of nutrients into host cells. Thus, they participate in the physiology of host plants through the function of specific genes encoded in their genome. AM fungi also modulate morphological adaptations and various physiological processes in host plants, that help to mitigate drought-induced injury and enhance drought tolerance. Several AM-specific host genes have been identified and reported to be responsible for conferring enhanced drought tolerance. This review provides an overview of the effect of drought stress on the diversity and activity of AM fungi, the symbiotic relationship that exists between AM fungi and host plants under drought stress conditions, elucidates the morphological, physiological, and molecular mechanisms underlying AM fungi-mediated enhanced drought tolerance in plants, and provides an outlook for future research. [ABSTRACT FROM AUTHOR]

An important question that is being increasingly studied across subdisciplines of Heliophysics is “how do mesoscale phenomena contribute to the global response of the system?” This review paper focuses on this question within two specific but interlinked regions in Near-Earth space: the magnetotail’s transition region to the inner magnetosphere and the ionosphere. There is a concerted effort within the Geospace Environment Modeling (GEM) community to understand the degree to which mesoscale transport in the magnetotail contributes to the global dynamics of magnetic flux transport and dipolarization, particle transport and injections contributing to the storm-time ring current development, and the substorm current wedge. Because the magnetosphere-ionosphere is a tightly coupled system, it is also important to understand how mesoscale transport in the magnetotail impacts auroral precipitation and the global ionospheric system response. Groups within the Coupling, Energetics and Dynamics of Atmospheric Regions Program (CEDAR) community have also been studying how the ionosphere-thermosphere responds to these mesoscale drivers. These specific open questions are part of a larger need to better characterize and quantify mesoscale “messengers” or “conduits” of information—magnetic flux, particle flux, current, and energy—which are key to understanding the global system. After reviewing recent progress and open questions, we suggest datasets that, if developed in the future, will help answer these questions.

Inter-hemispheric asymmetry (IHA) in Earth’s ionosphere–thermosphere (IT) system can be associated with high-latitude forcing that intensifies during storm time, e.g., ion convection, auroral electron precipitation, and energy deposition, but a comprehensive understanding of the pathways that generate IHA in the IT is lacking. Numerical simulations can help address this issue, but accurate specification of high-latitude forcing is needed. In this study, we utilize the Active Magnetosphere and Planetary Electrodynamics Response Experiment-revised fieldaligned currents (FACs) to specify the high-latitude electric potential in the Global Ionosphere and Thermosphere Model (GITM) during the October 8–9, 2012, storm. Our result illustrates the advantages of the FAC-driven technique in capturing high-latitude ion drift, ion convection equatorial boundary, and the storm-time neutral density response observed by satellite. First, it is found that the cross-polar-cap potential, hemispheric power, and ion convection distribution can be highly asymmetric between two hemispheres with a clear By dependence in the convection equatorial boundary. Comparison with simulation based on mirror precipitation suggests that the convection distribution is more sensitive to FAC, while its intensity also depends on the ionospheric conductance-related precipitation. Second, the IHA in the neutral density response closely follows the IHA in the total Joule heating dissipation with a time delay. Stronger Joule heating deposited associated with greater high-latitude electric potential in the southern hemisphere during the focus period generates more neutral density as well, which provides some evidences that the high-latitude forcing could become the dominant factor to IHAs in the thermosphere when near the equinox. Our study improves the understanding of storm-time IHA in high-latitude forcing and the IT system.

Sedation is recommended by most guidelines to be offered to all patients undergoing diagnostic flexible bronchoscopy (DFB) without contraindications, and the most commonly reported regimen is midazolam in combination with a short-acting opioid (fentanyl or alfentanil) to provide both sedative and antitussive effects. However, the optimal dose or ideal regimen of the combination therapy with midazolam and opioids has not yet been found. So this randomized, double-blinded clinical trial was designed and registered (ChiCTR2100049052) to assess the safety and efficacy of midazolam combined with different doses of alfentanil in DFB sedation. Our study showed that relative high doses of alfentanil (10–25 μg/kg) combined with a fixed low dose of midazolam can markedly reduce hemodynamic fluctuations, cough reactions, patients’ discomforts, and improve their satisfaction in a dose-dependent manner during DFB, with no significant increase in the desaturation risks.

This study investigated the associations between pet-ownership on nature engagement, interpersonal relationships, and well-being among 471 Taiwanese children aged 11–12, across different genders. The findings revealed that interactions with pets, primarily in the form of caregiving, enhanced empathy toward nature, notably among female participants from various racial and ethnic backgrounds, although direct contact with nature was generally limited. In terms of interpersonal relationships, family bonds were significant, with boys reporting stronger connections. Children who had previously or were currently owning pets displayed increased empathy toward the natural environment. The study highlighted a significant predictive relationship between children’s connection to nature and their development of interpersonal relationships, with peer relationships being particularly influential in predicting children’s well-being. These results underscored the importance of pet caregiving and peer interactions in the emotional and social development of children.

Clinically, air insoles may be applied to shoes to decrease plantar pressure gradient (PPG) and increase plantar gradient angle (PGA) to reduce foot ulcers. PPG and PGA may cause skin breakdown. The effects of different inner pressures of inflatable air insoles on dynamic PPG and PGA distributions are largely unknown in non-diabetics and people with diabetes. This study aimed to explore the impact of varying inner air insole pressures on PPG and PGA to establish early mitigation strategies for people at risk of foot ulcers. A repeated measures study design, including three air insoles (80 mmHg, 160 mmHg, and 240 mmHg) and two walking durations (10 and 20 min) for a total of six walking protocols, was tested on 13 healthy participants (height, 165.8 ± 8.4 cm; age, 27.0 ± 7.3 years; and weight, 56.0 ± 7.9 kg, BMI: 20.3 ± 1.7 kg/m^2) over three consecutive weeks. PPG, a measurement of the spatial variation in plantar pressure around the peak plantar pressure (PPP) and PGA, a variation in the gradient direction values at the three plantar regions, big toe (T1), first metatarsal head (M1), and second metatarsal head (M2), were calculated. This study indicated that PPG was lower at 80 mmHg air insoles after 20 min of walking in the M1 region (p = 0.010). The PGA in the M2 increased at an air insole of 80 mmHg compared to 240 mmHg (p = 0.015). Compared to 20 min, the 10 min walking duration at 240 mmHg of air insole had the lowest PPG in the M1 (p = 0.015) and M2 (p = 0.034) regions. The 80 mmHg air insole significantly lowered the PPG compared to a 160 mmHg and 240 mmHg air insole. Moreover, the 80 mmHg air insole significantly decreased PPP and increased PGA compared to the 160 mmHg and 240 mmHg air insole. A shorter walking period (10 min) significantly lowered PPG. The findings of this study suggest that people with a higher risk of foot ulcers should wear softer air insoles to have a lower PPG, as well as an increased PGA.

The absorption of shortwave irradiance in snow depends on the physical properties of snow (e.g., snow grain size and shape, liquid water content, etc.) and light-absorbing particles (LAP). Originating from natural and anthropogenic sources, LAP has been reported to accelerate snowmelt significantly in different regions globally. Yet, our process-level understanding of LAP after deposition onto snow remains rather limited. Here we investigate the impacts of artificial deposition of different LAP onto snow surfaces in an outdoor environment of northern Finland. Following LAP dry deposition into a custom-made tent standing on top of the snowpack, the albedo was followed along with the properties of snow in snow pit measurements throughout the spring season. The results showed that the albedo decay at the end of the season for the different spots were linked to the initial amount and type of LAP that were deposited onto the snowpack. Measured snow temperature profiles from LAP doped snow versus natural reference snow illustrated that the LAP affected snow had higher temperatures in the subsurface snow layers. Collected snow samples analyzed for size distribution of soot particles revealed no apparent agglomeration of soot particles during thaw-freezing events taking place during the experiment. Despite the relatively large perturbation of the experimentally deposited LAP, their impact on the season length was only up to 3 days. Additional experiments are, nevertheless, needed to better constrain the effects of LAP on snow albedo, melt rate, and other associated processes.

Background: The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. In the present study, we investigated whether mTORC1 signaling pathway mediates synapse loss induced by chronic stress in the hippocampus.Methods: Chronic restraint stress-induced depression-like behaviors were tested by behavior tests (sucrose preference test, forced swim test and tail suspension test). Synaptic proteins and alternations of phosphorylation levels of mTORC1 signaling-associated molecules were measured using Western blotting. In addition, mRNA changes of immediate early genes (IEGs) and glutamate receptors were measured by RT-PCR. Rapamycin was used to explore the role of mTORC1 signaling in the antidepressant effects of fluoxetine.Results: After successfully establishing the chronic restraint stress paradigm, we observed that the mRNA levels of some IEGs were significantly changed, indicating the activation of neurons and protein synthesis alterations. Then, there was a significant downregulation of glutamate receptors and postsynaptic density protein 95 at protein and mRNA levels. Additionally, synaptic fractionation assay revealed that chronic stress induced synapse loss in the dorsal and ventral hippocampus. Furthermore, these effects were associated with the mTORC1 signaling pathway-mediated protein synthesis, and subsequently the phosphorylation of associated downstream signaling targets was reduced after chronic stress. Finally, we found that intracerebroventricular infusion of rapamycin simulated depression-like behavior and also blocked the antidepressant effects of fluoxetine.Conclusion: Overall, our study suggests that mTORC1 signaling pathway plays a critical role in mediating synapse loss induced by chronic stress, and has part in the behavioral effects of antidepressant treatment.

This study aimed to characterize 16S rRNA methylase genes among Salmonella and to elucidate the structure and evolution of rmtB-carrying plasmids. One hundred fifty-eight Salmonella isolates from one pig slaughterhouse were detected as containing 16S rRNA methylase genes; two (1.27%) Salmonella London isolates from slaughtered pigs were identified to carry rmtB. They were resistant to gentamicin, amikacin, streptomycin, ampicillin, tetracycline, florfenicol, ciprofloxacin, and sulfamethoxazole/trimethoprim. The complete sequences of RmtB-producing isolates were obtained by PacBio single-molecule real-time sequencing. The isolate HA1-SP5 harbored plasmids pYUHAP5-1 and pYUHAP5-2. pYUHAP5-1 belonged to the IncFIBK plasmid and showed high similarity to multiple IncFIBK plasmids from Salmonella London in China. The rmtB-carrying plasmid pYUHAP5-2 contained a typical IncN-type backbone; the variable region comprising several resistance genes and an IncX1 plasmid segment was inserted in the resolvase gene resP and bounded by IS26. The sole plasmid in HA3-IN1 designated as pYUHAP1 was a cointegrate of plasmids from pYUHAP5-1-like and pYUHAP5-2-like, possibly mediated by IS26 via homologous recombination or conservative transposition. The structure differences between pYUHAP1 and its corresponding part of pYUHAP5-1 and pYUHAP5-2 may result from insertion, deletion, or recombination events mediated by mobile elements (IS26, ISCR1, and ISKpn43). This is the first report of rmtB in Salmonella London. IncN plasmids are efficient vectors for rmtB distribution and are capable of evolving by reorganization and cointegration. Our results further highlight the important role of mobile elements, particularly IS26, in the dissemination of resistance genes and plasmid evolution.