Clinical study of the effect of 5 kinds of antiepileptic drugs on the postictal state.

OBJECTIVE: To compare the effects of levetiracetam（LEV）, lamotrigine(LTG), oxcarbazepine(OXC), topiramate(TPM) and valproate (VPA) on postictal state (PIS). METHODS: A total of 187 epilepsy patients undergoing monotherapy were enrolled in a long-term follow-up study at the Affiliated Hospital of Yangzhou College. This included 30 patients on levetiracetam, 41 on valproate, 30 on oxcarbazepine, 28 on topiramate, and 31 on lamotrigine. A control group of 28 newly diagnosed or previously untreated epilepsy patients was also included. The Liverpool Seizure Severity Scale 2.0 (LSSS2.0) and the Seizure Severity Questionnaire (SSQ) were utilized to evaluate the patients' condition, with comparison based on the results of the postictal status items. EEG during PIS termination was assessed using the Grand Total EEG score (GTE) as an objective tool to measure the impact of Antiseizure medications (ASMs) on the post-seizure state. RESULTS: The LSSS2.0 score indicated a statistically significant difference in post-seizure status score among the 5 groups (p < 0.05). The difference between the 5 groups and the control group was statistically significant (p < 0.05). Results of the SSQ demonstrated that all 5 drugs significantly reduced the post-seizure status score compared to the control group (p < 0.05). The GTE score revealed that, in the later stage of the seizure, the GTE score of the levetiracetam group, valproate group, oxcarbazepine group, and lamotrigine group significantly decreased compared to the control group (P < 0.05). There was no significant decrease in the GTE score in the topiramate group (P < 0.05). CONCLUSION: Levetiracetam, lamotrigine, oxcarbazepine, topiramate, and valproate demonstrate favorable efficacy in ameliorating the severity of post-seizure condition. Further investigations are warranted to assess the potential of other widely employed anti-seizure medications in enhancing post-seizure status.

From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective.

Background: Acute kidney injury (AKI) is a severe condition marked by rapid renal function deterioration and elevated mortality, with traditional biomarkers lacking sensitivity and specificity. Rare tubulointerstitial diseases encompass a spectrum of disorders, primarily including monogenic diseases, immune-related conditions, and drug-induced tubulointerstitial diseases. The clinical manifestations vary from electrolyte and acid-base imbalances to kidney function insufficiency, which is associated with AKI in up to 20% of cases. Evidence indicated that rare tubulointerstitial diseases might provide new conceptual insights and perspectives for novel biomarkers and potential therapeutic strategies for AKI. Summary: Autosomal dominant tubulointerstitial kidney disease (ADTKD) and Fanconi syndrome (FS) are rare tubulointerstitial diseases. In ADTKD, UMOD and REN are closely related to AKI by affecting oxidative stress and tubuloglomerular feedback, which provide potential new biomarkers for AKI. Both rare tubulointerstitial diseases and AKI share etiologies and treatment responses. From the mechanism standpoint, rare tubulointerstitial diseases and AKI involve tubular transporter injury, initially manifesting as tubular dysfunction in tubulointerstitial disorder and progressing to AKI because of the programmed cell death with apoptosis, pyroptosis, or necroptosis of proximal tubule cells. Additionally, mitochondrial dysfunction has been identified as a common mechanism in both tubulointerstitial diseases and AKI induced by drugs, pSS, or monoclonal diseases. In the end, both AKI and FS patients and animal models responded well to the therapy of the primary diseases. Key Messages: In this review, we describe an overview of ADTKD and FS to identify their associations with AKI. Mitochondrial dysfunction contributes to rare tubulointerstitial diseases and AKI, which might provide a potential therapeutic target.

Electrochemistry promotion of Fe(â ¢)/Fe(â ¡) cycle for continuous activation of PAA for sludge disintegration: Performance and mechanism.

In this study, electrochemistry was used to enhance the advanced oxidation of Fe(Ⅱ)/PAA (EC/Fe(Ⅱ)/PAA) to disintegrate waste activated sludge, and its performance and mechanism was compared with those of EC, PAA, EC/PAA and Fe(Ⅱ)/PAA. Results showed that the EC/Fe(Ⅱ)/PAA process effectively improved sludge disintegration and the concentrations of soluble chemical oxygen demand, polysaccharides and nucleic acids increased by 62.85%, 41.15% and 12.21%, respectively, compared to the Fe(Ⅱ)/PAA process. Mechanism analysis showed that the main active species produced in the EC/Fe(Ⅱ)/PAA process were •OH, R-O• and FeIVO2+. During the reaction process, sludge flocs were disrupted and particle size was reduced by the combined effects of active species oxidation, electrochemical oxidation and PAA oxidation. Furthermore, extracellular polymeric substances (EPS) was degraded, the conversion of TB-EPS to LB-EPS and S-EPS was promoted and the total protein and polysaccharide contents of EPS were increased. After sludge cells were disrupted, intracellular substances were released, causing an increase in nucleic acids, humic acids and fulvic acids in the supernatant, and resulting in sludge reduction. EC effectively accelerated the conversion of Fe(Ⅲ) to Fe(Ⅱ), which was conducive to the activation of PAA, while also enhancing the disintegration of EPS and sludge cells. This study provided an effective approach for the release of organic matter, offering significant benefits in sludge resource utilization.

Comparison of Outcomes in Obese Patients after Total Knee Arthroplasty with Neutral or Mild Varus: A Retrospective Study with 8-Year Follow-Up.

OBJECTIVES: Residual varus after total knee arthroplasty (TKA) can affect functional outcomes, which may worsen in the presence of obesity. However, no studies were found to compare the outcomes of obese patients involving postoperative residual mild varus or neutral. The aim of this study was to compare postoperative complications and prosthesis survival, and functional outcomes for knees of obese patients with neutral or mild varus after TKA. METHODS: We retrospectively reviewed 188 consecutive obese patients (body mass index ≥30 kg/m2) at our hospital who underwent TKA due to varus knee osteoarthritis from January 2010 to December 2015. The mechanical hip-knee-ankle axis angle was measured in all patients at admission and discharge. Knee functions were retrospectively assessed based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Knee Score (KS-KS), Knee Society Function Score (KS-FS), Forgotten Joint Score (FJS), and range of motion (ROM). Continuous data were compared between knees with neutral or mild varus alignment using analysis of Student's t test or variance or the Kruskal-Wallis test as appropriate. For multiple comparisons of outcomes, we used Bonferroni-Dunn method to adjust p-values. Categorical data were compared using the chi-squared test. RESULTS: Of the 156 knees in 137 obese patients who completed follow-up for a mean of 8.32 ± 1.47 years, 97 knees were corrected from varus to neutral and 54 knees were kept in mild residual varus. Patients with mild varus knees had significantly WOMAC (8.25 ± 8.637 vs. 14.97 ± 14.193, p = 0.009) and better FJS (86.03 ± 15.607 vs. 70.22 ± 30.031, p = 0.002). The two types of knees did not differ significantly in KS-KS, KS-FS, or ROM. Although one patient with a neutral knee had to undergo revision surgery, there was no significant difference between two groups. CONCLUSIONS: For obese patients with osteoarthritis, preservation of residual varus alignment after TKA can improve functional outcomes without compromising prosthesis survival.

GSTP alleviates acute lung injury by S-glutathionylation of KEAP1 and subsequent activation of NRF2 pathway.

Oxidative stress plays an important role in the pathogenesis of acute lung injury (ALI). As a typical post-translational modification triggered by oxidative stress, protein S-glutathionylation (PSSG) is regulated by redox signaling pathways and plays diverse roles in oxidative stress conditions. In this study, we found that GSTP downregulation exacerbated LPS-induced injury in human lung epithelial cells and in mice ALI models, confirming the protective effect of GSTP against ALI both in vitro and in vivo. Additionally, a positive correlation was observed between total PSSG level and GSTP expression level in cells and mice lung tissues. Further results demonstrated that GSTP inhibited KEAP1-NRF2 interaction by promoting PSSG process of KEAP1. By the integration of protein mass spectrometry, molecular docking, and site-mutation validation assays, we identified C434 in KEAP1 as the key PSSG site catalyzed by GSTP, which promoted the dissociation of KEAP1-NRF2 complex and activated the subsequent anti-oxidant genes. In vivo experiments with AAV-GSTP mice confirmed that GSTP inhibited LPS-induced lung inflammation by promoting PSSG of KEAP1 and activating the NRF2 downstream antioxidant pathways. Collectively, this study revealed the novel regulatory mechanism of GSTP in the anti-inflammatory function of lungs by modulating PSSG of KEAP1 and the subsequent KEAP1/NRF2 pathway. Targeting at manipulation of GSTP level or activity might be a promising therapeutic strategy for oxidative stress-induced ALI progression.

Polarized emission of Cs3Cu2I5 nanowires embedded in nanopores of an anodic aluminum oxide template.

Due to the intrinsic polarized emission property, polarized emissive materials with anisotropic nanostructures are expected to be potential substitutes for polarizers. Herein, by the template-assisted strategy, well-aligned lead-free metal halide Cs3Cu2I5 nanowire (NW) arrays are fabricated by evaporating the precursor ink in the anodic aluminum oxide (AAO) for polarized emission. The Cs3Cu2I5/AAO composite film emits highly polarized light with a degree of polarization (DOP) of 0.50. Furthermore, by changing the molar ratio of CsI/CuI, the stability of Cs3Cu2I5 precursor inks is improved. Finally, an ultraviolet (UV) light-emitting diode (LED) is adopted to pump the composite film to achieve a blue LED device. The reported Cs3Cu2I5/AAO composite film with highly polarized light emissions will have great potential for polarized emission applications such as liquid crystal display backlights, waveguides, and lasers.

Genome-Wide and Expression Pattern Analysis of the HIT4 Gene Family Uncovers the Involvement of GHHIT4_4 in Response to Verticillium Wilt in Gossypium hirsutum.

Chromatin remodelers are essential for regulating plant growth, development, and responses to environmental stresses. HIT4 (HEAT-INTOLERANT 4) is a novel stress-induced chromatin remodeling factor that has been less studied in abiotic stress and stress resistance, particularly in cotton. In this study, we conducted a comprehensive analysis of the members of the HIT4 gene family in Gossypium hirsutum using bioinformatics methods, including phylogenetic relationships, gene organization, transcription profiles, phylogenetic connections, selection pressure, and stress response. A total of 18 HIT4 genes were identified in four cotton species, with six HIT4 gene members in upland cotton. Based on the evolutionary relationships shown in the phylogenetic tree, the 18 HIT4 protein sequences were classified into four distinct subgroups. Furthermore, we conducted chromosome mapping to determine the genomic locations of these genes and visually represented the structural characteristics of HIT4 in G. hirsutum. In addition, we predicted the regulatory elements in HIT4 in G. hirsutum and conducted an analysis of repetitive sequences and gene collinearity among HIT4 in four cotton species. Moreover, we calculated the Ka/Ks ratio for homologous genes to assess the selection pressure acting on HIT4. Using RNA-seq, we explored the expression patterns of HIT4 genes in G. hirsutum and Gossypium barbadense. Through weighted gene co-expression network analysis (WGCNA), we found that GHHIT4_4 belonged to the MEblue module, which was mainly enriched in pathways such as DNA replication, phagosome, pentose and glucuronate interconversions, steroid biosynthesis, and starch and sucrose metabolism. This module may regulate the mechanism of upland cotton resistance to Verticillium wilt through DNA replication, phagosome, and various metabolic pathways. In addition, we performed heterologous overexpression of GH_D11G0591 (GHHIT4_4) in tobacco, and the results showed a significant reduction in disease index compared to the wild type, with higher expression levels of disease resistance genes in the transgenic tobacco. After conducting a VIGS (virus-induced gene silencing) experiment in cotton, the results indicated that silencing GHHIT4_4 had a significant impact, the resistance to Verticillium wilt weakened, and the internode length of the plants significantly decreased by 30.7% while the number of true leaves increased by 41.5%. qRT-PCR analysis indicated that GHHIT4_4 mainly enhanced cotton resistance to Verticillium wilt by indirectly regulating the PAL, 4CL, and CHI genes. The subcellular localization results revealed that GHHIT4_4 was predominantly distributed in the mitochondria and nucleus. This study offers preliminary evidence for the involvement of the GHHIT4_4 in cotton resistance to Verticillium wilt and lays the foundation for further research on the disease resistance mechanism of this gene in cotton.

Main Control Factors of Fracture Propagation in Reservoir: A Review.

The fracture distribution and internal control factors after the fracturing of unconventional oil and gas reservoirs determine the reservoir reforming effect to a large extent. Based on the research of global scholars on the influencing factors of fracture propagation, comprehensive theoretical model, and numerical simulation, this Review systematically discusses the influence of internal geological factors and external engineering factors of unconventional oil and gas reservoir on fracture propagation behavior and summarizes the current problems and development trends in fracture research. The results show the following: (1) The fracture propagation is a comprehensive process constrained by lithology and mineral composition, water saturation, nonhomogeneity, natural weak surface, and ground stress. (2) External engineering factors have a meaningful control effect on fracture propagation; the type and temperature of fracturing fluids can also change the mechanical properties of different rocks, thus affecting the fracture propagation pattern. (3) The existing fracture propagation models have certain limitations, and their computational reliability still needs to be further verified. (4) Numerical simulation can break through the limitations of physical simulation, but different simulation methods have different shortcomings and applicability. In the future, we should focus on: (1) finding parameters to quantitatively characterize heterogeneity at the 3D level, which is an important direction to study the effect of heterogeneity on fracture propagation; (2) introducing computerized methods to establish a geological model that considers multiple factors and combining it with numerical simulation software to study fracture propagation; (3) considering the characteristics of fluid-liquid-solid phase comprehensively, establishing a suitable THL coupling equation; (4) how the interaction mode of fracturing fracture is combined with the natural fracture geometry, and how the fracture is affected by fracturing engineering parameters such as fluid injection rate and viscosity of fracturing fluid; and (5) geology-engineering dynamic integration, which is an important direction to be carried out in the future.

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.

The hidden curves of risk: a nonlinear model of cumulative risk and school bullying victimization among adolescents with autism spectrum disorder.

BACKGROUND: School bullying victimization (SBV) occurs more frequently in students with autism spectrum disorder (ASD) in general education than in special classes, and there is a cumulative risk effect on SBV exposure among young people with ASD reported by their parents and teachers. However, SBV is a personal experience, the predictive patterns of cumulative risk on SBV reported by themselves and its psychological mechanism remain unclear. This study aims to explore the relationship between cumulative risk and SBV based on self-report, and to test whether internalizing problems mediates this relationship among adolescents with ASD placed in regular classes. METHODS: This study used data from the Taiwan Special Needs Education Longitudinal Study (SNELS) in 2011. The analysis included 508 adolescents with ASD who were in regular classes across Taiwan. The primary variables under study were the quality of friendship interactions, teacher-student relationship, school connection, perceived stigma, the impact caused by the disabilities, internalizing problem, and whether the participants had experienced SBV over the past semester, while control variables were adaptability and social-emotional skills. Established risk factors were summed to form a cumulative risk score. RESULTS: The cumulative risk was positively associated with SBV. The relationship was characterized by the nonlinear pattern of the quadratic function (negative acceleration model) between cumulative risk and SBV. Internalizing problem played a partial mediating role in the effect of cumulative risk on SBV. CONCLUSIONS: Intervention measures to reduce SBV should include the strategies to reduce the number of risks to which adolescents with ASD in regular classes are exposed, comprehensive prevention targeting each risk factor is needed specially when the number of risks is one or two, and more attention needs to be given to their internalizing problem in various ways.

The burden of vision loss due to cataract in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To provide a reference for future policy and measure formulation by conducting a detailed analysis of the burden of vision loss due to cataract by year, age, and gender in China from 1990 to 2019. METHODS: Data on the prevalence and disability-adjusted life-years (DALYs) due to cataract in China and neighboring and other G20 countries were extracted from the 2019 Global Burden of Disease (GBD) study to observe the changing trends of vision loss. RESULTS: The number and rate of all-age prevalence and DALYs for cataract in China increased significantly from 1990 to 2019. The age-standardized DALYs rate witnessed a slowly declining trend by 10.16%. And the age-standardized prevalence increased by 14.35% over the 30-year period. Higher prevalence and DALYs were observed in female population from 1990 through 2019, with little improvement over the decades(all p < 0.001). The disease burden of cataract is higher in middle-aged and elderly people. Blindness accounted for the largest proportion of vision impairment burden caused by cataract in China. The age-standardized prevalence and DALY rate of cataract in China were lower than those in India and Pakistan, but higher than those in Russia, South Korea, North Korea, Singapore, and Japan. CONCLUSIONS: In the past 30 years, although the age-standardized DALYs rate has decreased slightly in China, the all-age prevalence and DALYs have both increased. This study highlights the importance of reducing cataract burden by providing timely and easily accessible quality care, especially in females and the elderly population.

Inhibition of miR-29a-3p Alleviates Apoptosis of Lens Epithelial Cells via Upregulation of CAND1.

PURPOSE: Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved. METHODS: In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis. RESULT: Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p. CONCLUSION: These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts.

Outcomes of culture-negative or -positive periprosthetic joint infections: A systematic review and meta-analysis.

OBJECTIVES: This study overviewed the current database of studies on periprosthetic joint infections (PJIs) to compare outcomes and antibiotic side effects in culture-negative or culture-positive PJIs and assess treatment options for culture-negative PJIs. PATIENTS AND METHODS: A systematic review and meta-analysis was undertaken using studies published before July 2022 in MEDLINE, EMBASE, and Cochrane Library. All studies comparing treatment of culture-negative or -positive PJIs were included. Afterward, the infection control rate, periprosthetic or spacer fracture, hip joint or spacer dislocation, and antibiotic side effects in different treatment methods of PJI were analyzed. RESULTS: Eleven studies involving 1,747 patients were included. Most studies clearly defined the infection control criteria: no pain or swelling, no wound drainage, normal serology, and normal radiographic findings. Patients were followed until treatment failure, death, or until the last clinical visit without evidence of treatment failure. The two types of PJIs did not differ significantly in infection control rates (culture-negative PJI 79.2% vs. culture-positive PJI 76.6%; odds ratio [OR]=1.20, 95% confidence interval [CI]: 0.84 to 1.70), either after all types of surgical treatment or after two-stage revision arthroplasty (OR=1.12, 95% CI: 0.72 to 1.75), single-stage revision arthroplasty (OR=0.51, 95% CI: 0.19 to 1.37), or debridement, antibiotics, and implant retention (OR=0.88, 95% CI: 0.50 to 1.54). Similarly, we did not find differences in periprosthetic or spacer fracture and hip joint or spacer dislocation. For culture-negative PJIs, the infection control rate was 85.2% after two-stage revision arthroplasty, 90.6% after single-stage revision arthroplasty, and 69.7% after debridement, antibiotics, and implant retention. Data pooled from three studies showed higher incidence of antibiotic side effects for culture-negative PJIs. CONCLUSION: The clinical outcomes of one-stage revision and two-stage revision are comparable. Therefore, both of them can be considered in surgical treatment for culture-negative PJIs. In addition, limited data showed a higher incidence of antibiotic side effects in culture-negative PJIs.

Host plant-mediated effects on Buchnera symbiont: implications for biological characteristics and nutritional metabolism of pea aphids (Acyrthosiphon pisum).

Introduction: The pea aphid, Acyrthosiphon pisum, is a typical sap-feeding insect and an important worldwide pest. There is a primary symbiont-Buchnera aphidicola, which can synthesize and provide some essential nutrients for its host. At the same time, the hosts also can actively adjust the density of bacterial symbiosis to cope with the changes in environmental and physiological factors. However, it is still unclear how symbionts mediate the interaction between herbivorous insects' nutrient metabolism and host plants. Methods: The current study has studied the effects of different host plants on the biological characteristics, Buchnera titer, and nutritional metabolism of pea aphids. This study investigated the influence of different host plants on biological characteristics, Buchnera titer, and nutritional metabolism of pea aphids. Results and discussion: The titer of Buchnera was significantly higher on T. Pretense and M. officinalis, and the relative expression levels were 1.966±0.104 and 1.621±0.167, respectively. The content of soluble sugar (53.46±1.97µg/mg), glycogen (1.12±0.07µg/mg) and total energy (1341.51±39.37µg/mg) of the pea aphid on V. faba were significantly higher and showed high fecundity (143.86±11.31) and weight (10.46±0.77µg/mg). The content of total lipids was higher on P. sativum and T. pretense, which were 2.82±0.03µg/mg and 2.92±0.07µg/mg, respectively. Correlation analysis found that the difference in Buchnera titer was positively correlated with the protein content in M. officinalis and the content of total energy in T. pratense (P < 0.05). This study confirmed that host plants not only affected the biological characteristics and nutritional metabolism of pea aphids but also regulated the symbiotic density, thus interfering with the nutritional function of Buchnera. The results can provide a theoretical basis for further studies on the influence of different host plants on the development of pea aphids and other insects.

Overexpression of Glutathione S-Transferases in Human Diseases: Drug Targets and Therapeutic Implications.

Glutathione S-transferases (GSTs) are a major class of phase II metabolic enzymes. Besides their essential role in detoxification, GSTs also exert diverse biological activities in the occurrence and development of various diseases. In the past few decades, much research interest has been paid to exploring the mechanisms of GST overexpression in tumor drug resistance. Correspondingly, many GST inhibitors have been developed and applied, solely or in combination with chemotherapeutic drugs, for the treatment of multi-drug resistant tumors. Moreover, novel roles of GSTs in other diseases, such as pulmonary fibrosis and neurodegenerative diseases, have been recognized in recent years, although the exact regulatory mechanisms remain to be elucidated. This review, firstly summarizes the roles of GSTs and their overexpression in the above-mentioned diseases with emphasis on the modulation of cell signaling pathways and protein functions. Secondly, specific GST inhibitors currently in pre-clinical development and in clinical stages are inventoried. Lastly, applications of GST inhibitors in targeting cell signaling pathways and intracellular biological processes are discussed, and the potential for disease treatment is prospected. Taken together, this review is expected to provide new insights into the interconnection between GST overexpression and human diseases, which may assist future drug discovery targeting GSTs.

Determination of the Lower Limit of Physical Properties of Tight Oil Reservoirs: A Case Study of the Lower Es3 in the Jiangjiadian Area, Linnan Sag.

The tight oil reservoir in Linnan Sag has great potential, a wide distribution range, and large total predicted resources. The rapid accumulation and burial of sediments in multiple source directions have resulted in the characteristics of low porosity and low permeability of the Lower Es3 in the Jiangjiadian area, Linnan Sag. Based on conventional core analysis data, mercury injection data, and oil testing data, this paper comprehensively determines the lower limit of effective physical properties of reservoirs in the Jiangjiadian area of Linnan Sag and studies its main influencing factors. The results show that (1) the lower Es3 reservoir in the Jiangjiadian area of Linnan Sag mainly develops feldspar sandstone and lithic feldspar sandstone. The porosity is mainly distributed at about 12%, and the permeability is mainly distributed at 0.3 mD; (2) based on the study of reservoir characteristics, the empirical statistical method based on core analysis data and the pore-permeability intersection method, the mercury injection parameter method based on test data, and the oil test verification method are used to comprehensively determine the lower limit of physical properties in the study area. The lower limit of porosity is 7.87%, and the lower limit of permeability is 0.16 mD; (3) sedimentation mainly affects the lower limit of physical properties by controlling reservoir lithology and pore structure. The existence of compaction and cementation in diagenesis will reduce the reservoir porosity and affect the lower limit of effective physical properties. The secondary dissolution pores formed by dissolution have a certain improvement effect on the effective physical properties of the reservoir.

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

Background: Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC. Methods: We explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes. Results: Microbial α and ß diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001). Conclusion: Our study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.

Multiview intelligent networking based on the genetic evolution algorithm for precise 3D measurements.

The use of multi-visual network 3D measurements is increasing; however, finding ways to apply low-cost industrial cameras to achieve intelligent networking and efficient measurement is a key problem that has not been fully solved. In this paper, the multivision stereo vision 3D measurement principle and multivision networking process constraints are analyzed in depth, and an intelligent networking method based on the genetic evolution algorithm (GEA) is proposed. The genetic operation is improved, and the fitness function is dynamically calibrated. Based on the visual sphere model, the best observation distance is assigned as the radius of the visual sphere, and the required constraints are fused to establish an intelligent networking design of the centering multivision. A simulation and experiment show that the proposed algorithm is widely feasible, and its measurement accuracy meets the requirements of the industrial field. Our multiview intelligent networking algorithms and methods provide solid theoretical and technical support for low-cost and efficient on-site 3D measurements of industrial structures.

Unraveling a Combined Inactivation Mechanism of Cytochrome P450s by Genipin, the Major Reactive Aglycone Derived from Gardeniae Fructus.

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.