Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve. Results Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87－0.97), 0.89 (95% CI, 0.81－0.94), 8.43 (95% CI, 4.81－14.78), 0.07 (95% CI, 0.03－0.15), and 118.86 (95% CI, 44.18－319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95－0.98). Conclusions Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicenter Real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analysed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% versus [vs.] 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P=0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P=0.694) and proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P=0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P=0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence (odds ratio 0.62 [95% CI 0.41-0.92]; P=0.018). No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P=0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates, and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35.

Objectives: Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. Methods: We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. Results: The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. Conclusion: CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

Conjunctive encoding of exploratory intentions and spatial information in the hippocampus.

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

Large-scale kinetic simulations of colliding plasmas within a hohlraum of indirect-drive inertial confinement fusion.

The National Ignition Facility has recently achieved successful burning plasma and ignition using the inertial confinement fusion (ICF) approach. However, there are still many fundamental physics phenomena that are not well understood, including the kinetic processes in the hohlraum. Shan et al. [Phys. Rev. Lett. 120, 195001 (2018)0031-900710.1103/PhysRevLett.120.195001] utilized the energy spectra of neutrons to investigate the kinetic colliding plasma in a hohlraum of indirect drive ICF. However, due to the typical large spatial-temporal scales, this experiment could not be well simulated by using available codes at that time. Utilizing our advanced high-order implicit PIC code, LAPINS, we were able to successfully reproduce the experiment on a large scale of both spatial and temporal dimensions, in which the original computational scale was increased by approximately seven to eight orders of magnitude. Not only is the validity of the explanation of the experiment confirmed by our simulations, i.e., the abnormally large width of neutron spectra comes from beam-target nuclear fusions, but also a different physical insight into the source of energetic deuterium ions is provided. The acceleration of deuterium ions can be categorized into two components: one is propelled by a sheath electric field created by the charge separation at the onset, while the other is a result of the reflection of the potential of the shock wave. The robustness of the acceleration mechanism is analyzed with varying initial conditions, e.g., temperatures, drifting velocity, and ion components. This paper might serve as a reference for benchmark simulations of upcoming simulation codes and may be relevant for future research on mixtures and entropy increments at plasma interfaces.

Enhancing the Efficiency and Stability of Tin-Lead Perovskite Solar Cells via Sodium Hydroxide Dedoping of PEDOT:PSS.

Tin-lead (Sn-Pb) perovskite solar cells (PSCs) have gained interest as candidates for the bottom cell of all-perovskite tandem solar cells due to their broad absorption of the solar spectrum. A notable challenge arises from the prevalent use of the hole transport layer, PEDOT:PSS, known for its inherently high doping level. This high doping level can lead to interfacial recombination, imposing a significant limitation on efficiency. Herein, NaOH is used to dedope PEDOT:PSS, with the aim of enhancing the efficiency of Sn-Pb PSCs. Secondary ion mass spectrometer profiles indicate that sodium ions diffuse into the perovskite layer, improving its crystallinity and enlarging its grains. Comprehensive evaluations, including photoluminescence and nanosecond transient absorption spectroscopy, confirm that dedoping significantly reduces interfacial recombination, resulting in an open-circuit voltage as high as 0.90 V. Additionally, dedoping PEDOT:PSS leads to increased shunt resistance and high fill factor up to 0.81. As a result of these improvements, the power conversion efficiency is enhanced from 19.7% to 22.6%. Utilizing NaOH to dedope PEDOT:PSS also transitions its nature from acidic to basic, enhancing stability and exhibiting less than a 7% power conversion efficiency loss after 1176 h of storage in N2 atmosphere.

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Acute effects of different Tai Chi practice protocols on cardiac autonomic modulation.

Tai Chi serves as an effective exercise modality for enhancing autonomic regulation. However, a majority of existing studies have employed the single routine (SR) protocol as the basis for health interventions. The extent to which the gong routine application (GRA) protocol achieves similar levels of exercise load stimulation as traditional single practice routines remains uncertain. Therefore, this study the distinct characteristics of autonomic load stimulation in these different protocols, thus providing a biological foundation to support the development of Tai Chi health promotion intervention programs. we recruited a cohort of forty-five university students to participate in the 15 min GRA protocol and SR protocol. We collected heart rate and heart rate variability indicators during periods of rest, GRA protocol, and SR protocol utilizing the Polar Scale. Additionally, we assessed the mental state of the participants using the BFS State of Mind Scale. In summary, the autonomic load is lower in the GRA protocol compared to the SR protocol, with lower sympathetic activity but higher parasympathetic activity in the former. Results are specific to college students, additional research is necessary to extend support for frail older adults. It is advised to incorporate GRA protocol alongside SR protocol in Tai Chi instruction. This approach is likely to enhance Tai Chi skills and yield greater health benefits.

Selective removal of Cr2O72- in aqueous solution by nonporous pure crystals of cucurbit[6]uril.

Cucurbit[6]uril (Q[6]) could serve as a selective absorbent for the toxic anion Cr2O72-, which was demonstrated by the results of UV-vis, ICP, XPS, SEM, and EDS experiments. Single-crystal X-ray diffraction analysis revealed that capture capacity could be attributed to the outer-surface interactions of cucurbit[n]uril between Cr2O72- and the outer surface of Q[6].

High quality assemblies of four indigenous chicken genomes and related functional data resources.

Many lines of evidence indicate that red jungle fowl (RJF) is the primary ancestor of domestic chickens. Although multiple versions of RJF (galgal2-galgal5 and GRCg6a) and commercial chickens (GRCg7b/w and Huxu) genomes have been assembled since 2004, no high-quality indigenous chicken genomes have been assembled, hampering the understanding of chicken domestication and evolution. To fill the gap, we sequenced the genomes of four indigenous chickens with distinct morphological traits in southwest China, using a combination of short, long and Hi-C reads. We assembled each genome (~1.0 Gb) into 42 chromosomes with chromosome N50 90.5-90.9 Mb, amongst the highest quality of chicken genome assemblies. To provide resources for gene annotation and functional analysis, we also sequenced transcriptomes of 10 tissues for each of the four chickens. Moreover, we corrected many mis-assemblies and assembled missing micro-chromosomes 29 and 34-39 for GRCg6a. Our assemblies, sequencing data and the correction of GRCg6a can be valuable resources for studying chicken domestication and evolution.

Multifunctional Electrostatic Droplet Manipulation on the Femtosecond Laser-Prepared Slippery Surfaces.

A strategy to manipulate droplets on the lubricated slippery surfaces using tribostatic electricity is proposed. By employing femtosecond laser-induced porous microstructures, we prepared a slippery surface with ultralow adhesion to various liquids. Electrostatic induction causes the charges within the droplet to be redistributed; thus, the droplet on the as-prepared slippery surfaces can be guided by electrostatic force under the electrostatic field, with controllable sliding direction and unlimited transport distance. The combination of electrostatic interaction and slippery surfaces allows us to manipulate droplets with a wide volume range (from 100 nL to 0.5 mL), charged droplets (including electrostatic attraction and repulsion), corrosive droplets, and even organic droplets with ultralow surface tension. In addition, droplets on tilted surfaces, curved surfaces, and inverted slippery surfaces can also be manipulated. Especially, the slippery surfaces can even allow the electrostatic interaction to manipulate alcohol with surface tension as low as 22.3 mN/m and liquid droplets suspended on a downward surface, which is not possible with reported superhydrophobic substrates. The features of slippery surfaces make the electrostatic manipulation successfully applied in versatile droplet manipulation, droplet patterning, chemical microreaction, transport of solid cargo, targeted delivery of chemicals, and liquid sorting.

EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47.

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

Exercise intervention in middle-aged and elderly individuals with insomnia improves sleep and restores connectivity in the motor network.

Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P < 0.001) compared to that in the waitlist group. We also found increased functional connectivity of the motor network with the cerebellum in the exercise group (P < 0.001). Moreover, we observed significant correlations between improvement in subjective sleep indices and connectivity changes within the motor network. We highlight exercise-induced improvement in sleep quality and functional plasticity of the aging brain.

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). However, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear. AIM: To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders. METHODS: Liver samples were collected from 16 healthy donors (HDs) and 17 advanced HBV-ACLF patients who were eligible for liver transplantation. The mitochondrial ultrastructure, metabolic characteristics, and immune microenvironment of the liver were assessed. More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF. RESULTS: Compared with HDs, there was extensive hepatocyte necrosis, immune cell infiltration, and ductular reaction in patients with ACLF. In patients, the liver suffered severe hypoxia, as evidenced by increased expression of hypoxia-inducible factor-1α. Swollen mitochondria and cristae were observed in the liver of patients. The number, length, width, and area of mitochondria were adaptively increased in hepatocytes. Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased, while anaerobic glycolysis was enhanced in patients with HBV-ACLF. These findings suggested that, to a greater extent, hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source. Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate, which stimulates peripheral monocyte infiltration into the liver. Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68+ HLA-DR+ macrophages and elevated levels of both interleukin-1ß and transforming growth factor-ß1 in their livers. The abundance of CD206+ CD163+ macrophages and expression of interleukin-10 decreased. The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines. CONCLUSION: The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling, leading to advanced HBV-ACLF. These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.

Research on the Properties of Wasteforms after Direct Involvement of Uranium-Containing Silica Gel in Glass Network Formation.

Uranium-containing silica gel (UCSG) is a secondary waste generated during the advanced treatment of nuclear wastewater. In order to reduce the growing storage pressure for UCSG, from the perspective of building a borosilicate glass network, UCSG was used to replace SiO2 in the glass-cured formula to directly achieve the immobilization of UCSG. SEM-EDS results showed that uranium was uniformly distributed in the matrix, and the maximum solid solubility of UCSG (two components: silica gel and uranyl ions) in the formula was as high as 55 wt %. At the same time, TG-MS proved that silica gel lost OH groups (down about 4.61 wt %) and formed Si-O-Si bond by condensation. FT-IR and XPS proved a change in the number of Si-O-Si bond, and new Si-O-B and Si-O-Al bond appeared on the spectrum. This was evidence that silica gel could self-involved participate in the construction of glass networks. EPR analysis obtained the changes in the coordination environment of U atom, the U atom decreased spin electrons number in the glass than in uranyl crystals. The glass also has good physical properties (hardness: 6.51 ± 0.23 GPa; density: 2.3977 ± 0.0056 g/cm3) and chemical durability (normalized leaching rate: LRU = 2.34 × 10-4 ± 2.05 × 10-6 g·m2·days-1 after 42 days), this research provided tactics for simple treatment of uranium-containing silica gel in one step.

Cyclin-dependent kinase inhibitor 1A inhibits pyroptosis to enhance human lung adenocarcinoma cell radioresistance by promoting DNA repair.

Purpose: One of the best anticancer treatments available is radiotherapy, which can be used either alone or in conjunction with other forms of treatment including chemotherapy and surgery. Nevertheless, a number of biochemical and physiological processes that react to ionizing radiation might provide tumor cells radioresistance, which makes radiotherapy ineffective. It has been found that CDKN1A regulates DNA damage repair, which contributes to tumor radioresistance. However, the precise mechanism is still unknown. Therefore, this study aimed to explore the mechanisms underlying CDKN1A-enhanced radioresistance in tumor cells. Methods: Cells were irradiated with 4 Gy after CDKN1A overexpression or knockdown. CDKN1A expression was measured using real-time PCR, cell viability was evaluated using cell counting kit-8 and colony formation assays, and cytotoxicity was assessed using a lactate dehydrogenase assay. Pyroptosis in cells was analyzed using caspase-1 activity assay, enzyme-linked immunosorbent assay, and flow cytometry. Inflammation activation was detected through a co-immunoprecipitation assay. Activation of pyroptosis-related proteins was analyzed using immunohistochemistry, Western blot, and immunofluorescence. Tumor radioresistance in vivo was evaluated in a mouse xenograft model. Results: Radiotherapy upregulated CDKN1A expression, which promoted lung adenocarcinoma cell survival. CDKN1A influenced radiation-induced pyroptosis in A549, which mainly depended on inhibiting the activation of the AIM2 inflammasome by promoting DNA repair. Additionally, CDKN1A upregulation enhanced A549 xenograft tumor radioresistance by inhibiting radiation-induced pyroptosis in vivo. Conclusions: CDKN1A inhibits pyroptosis to enhance the radioresistance of lung adenocarcinoma cells by promoting DNA repair. This study may serve as a reference for developing novel targeted therapies against cancer.