Development and Validation of a Machine Learning Prognostic Model of m5C Related immune Genes in Lung Adenocarcinoma.

BACKGROUND: The aim of this retrospective research was to develop an immune-related genes significantly associated with m5C methylation methylation (m5C-IRGs)-related signature associated with lung adenocarainoma (LUAD). METHODS: We introduced transcriptome data to screen out m5C-IRGs in The Cancer Genome Atlas (TCGA)-LUAD dataset. Subsequently, the m5C-IRGs associated with survival were certificated by Kaplan Meier (K-M) analysis. The univariate Cox, least absolute shrinkage and selection operator (LASSO) regression, and xgboost.surv tool were adopted to build a LUAD prognostic signature. We further conducted gene functional enrichment, immune microenvironment and immunotherapy analysis between 2 risk subgroups. Finally, we verified m5C-IRGs-related prognostic gene expression in transcription level. RESULTS: A total of 76 m5C-IRGs were identified in TCGA-LUAD dataset. Furthermore, 27 m5C-IRGs associated with survival were retained. Then, a m5C-IRGs prognostic signature was build based on the 3 prognostic genes (HLA-DMB, PPIA, and GPI). Independent prognostic analysis suggested that stage and RiskScore could be used as independent prognostic factors. We found that 4104 differentially expressed genes (DEGs) between the 2 risk subgroups were mainly concerned in immune receptor pathways. We found certain distinction in LUAD immune microenvironment between the 2 risk subgroups. Then, immunotherapy analysis and chemotherapeutic drug sensitivity results indicated that the m5C-IRGs-related gene signature might be applied as a therapy predictor. Finally, we found significant higher expression of PPIA and GPI in LUAD group compared to the normal group. CONCLUSIONS: The prognostic signature comprised of HLA-DMB, PPIA, and GPI based on m5C-IRGs was established, which might provide theoretical basis and reference value for the research of LUAD. PUBLIC DATASETS ANALYZED IN THE STUDY: TCGA-LUAD dataset was collected from the TCGA (https://portal.gdc.cancer.gov/) database, GSE31210 (validation set) was retrieved from GEO (https://www.ncbi.nlm.nih.gov/geo/) database.

A Distinct Metabolically Defined Central Nucleus Circuit Bidirectionally Controls Anxiety-Related Behaviors.

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeA neurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeA neurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeA neurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA-BNST). Optogenetic activation and inhibition of the sEHCeA-BNST pathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeA neurons underlying anxiety.SIGNIFICANCE STATEMENT Soluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeA neurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeA neurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.

The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function.

The NLRP3 inflammasome is a supramolecular complex that is linked to sterile and pathogen-dependent inflammation, and its excessive activation underlies many diseases. Ion flux disturbance and cell volume regulation are both reported to mediate NLRP3 inflammasome activation, but the underlying orchestrating signaling remains not fully elucidated. The volume-regulated anion channel (VRAC), formed by LRRC8 proteins, is an important constituent that controls cell volume by permeating chloride and organic osmolytes in response to cell swelling. We now demonstrate that Lrrc8a, the essential component of VRAC, plays a central and specific role in canonical NLRP3 inflammasome activation. Moreover, VRAC acts downstream of K+ efflux for NLRP3 stimuli that require K+ efflux. Mechanically, our data demonstrate that VRAC modulates itaconate efflux and damaged mitochondria production for NLRP3 inflammasome activation. Further in vivo experiments show mice with Lrrc8a deficiency in myeloid cells were protected from lipopolysaccharides (LPS)-induced endotoxic shock. Taken together, this work identifies VRAC as a key regulator of NLRP3 inflammasome and innate immunity by regulating mitochondrial adaption for macrophage activation and highlights VRAC as a prospective drug target for the treatment of NLRP3 inflammasome and itaconate related diseases.

Astrocytic Epoxyeicosatrienoic Acid Signaling in the Medial Prefrontal Cortex Modulates Depressive-like Behaviors.

Major depressive disorder is the most common mental illness. Mounting evidence indicates that astrocytes play a crucial role in the pathophysiology of depression; however, the underlying molecular mechanisms remain elusive. Compared with other neuronal cell types, astrocytes are enriched for arachidonic acid metabolism. Herein, we observed brain-region-specific alterations of epoxyeicosatrienoic acid (EET) signaling, which is an arachidonic acid metabolic pathway, in both a mouse model of depression and postmortem samples from patients with depression. The enzymatic activity of soluble epoxide hydrolase (sEH), the key enzyme in EET signaling, was selectively increased in the mPFC of susceptible mice after chronic social defeated stress and was negatively correlated with the social interaction ratio, which is an indicator of depressive-like behavior. The specific deletion of Ephx2 (encode sEH) in adult astrocytes induced resilience to stress, whereas the impaired EET signaling in the mPFC evoked depressive-like behaviors in response to stress. sEH was mainly expressed on lysosomes of astrocytes. Using pharmacological and genetic approaches performed on C57BL/6J background adult male mice, we found that EET signaling modulated astrocytic ATP release in vitro and in vivo Moreover, astrocytic ATP release was required for the antidepressant-like effect of Ephx2 deletion in adult astrocytes. In addition, sEH inhibitors produced rapid antidepressant-like effects in multiple animal models of depression, including chronic social defeated stress and chronic mild stress. Together, our results highlight that EET signaling in astrocytes in the mPFC is essential for behavioral adaptation in response to psychiatric stress.SIGNIFICANCE STATEMENT Astrocytes, the most abundant glial cells of the brain, play a vital role in the pathophysiology of depression. Astrocytes secrete adenosine ATP, which modulates depressive-like behaviors. Notably, astrocytes are enriched for arachidonic acid metabolism. In the present study, we explored the hypothesis that epoxyeicosatrienoic acid signaling, an arachidonic acid metabolic pathway, modulates astrocytic ATP release and the expression of depressive-like behaviors. Our work demonstrated that epoxyeicosatrienoic acid signaling in astrocytes in the mPFC is essential for behavioral homeostatic adaptation in response to stress, and the extent of astrocyte functioning is greater than expected based on earlier reports.

Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.

Astrocytes respond to CNS insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice. Interestingly, extensive astrogliosis without significant astrocyte proliferation and glial scar formation was observed in these mice. The inhibition of neuronal mTORC1 may activate astrogliosis by reducing neuron-derived fibroblast growth factor 2 (FGF-2), which might trigger FGF receptor signaling in astrocytes to maintain their nonreactive state, and FGF-2 injection successfully prevented astrogliosis in Raptor knock-out mice. This study demonstrates that neuronal mTORC1 inhibits reactive astrogliosis and plays an important role in CNS pathologies.

Astrocytic adenosine 5'-triphosphate release regulates the proliferation of neural stem cells in the adult hippocampus.

Astrocytes are key components of the niche for neural stem cells (NSCs) in the adult hippocampus and play a vital role in regulating NSC proliferation and differentiation. However, the exact molecular mechanisms by which astrocytes modulate NSC proliferation have not been identified. Here, we identified adenosine 5'-triphosphate (ATP) as a proliferative factor required for astrocyte-mediated proliferation of NSCs in the adult hippocampus. Our results indicate that ATP is necessary and sufficient for astrocytes to promote NSC proliferation in vitro. The lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficient ATP release from astrocytes. This deficiency led to a dysfunction in NSC proliferation that could be rescued via the administration of exogenous ATP. Moreover, P2Y1-mediated purinergic signaling is involved in the astrocyte promotion of NSC proliferation. As adult hippocampal neurogenesis is potentially involved in major mood disorder, our results might offer mechanistic insights into this disease.

Digital Eddy Current Detection Method Based on High-Speed Sampling with STM32.

The electromagnetic eddy current non-destructive testing system enables the non-destructive analysis of surface defect information on tested materials. Based on the principles of eddy current detection, this paper presents a digital eddy current detection method using high-speed sampling based on STM32. A differential eddy current coil is used as the detection probe, and the combination of a differential bridge and a differential amplifier circuit helps to reduce common-mode noise interference. The detection signal is collected via an STM32-based acquisition circuit and transmitted to the host computer through Ethernet for digital demodulation processing. The host computer performs operations such as smoothing averaging, sinusoidal fitting, and outlier removal to extract the amplitude and phase of the detection signal. The system also visually displays the condition of the tested object's surface in real time through graphical visualization. Testing showed that this system can operate at frequencies up to 8.84 MHz and clearly identify defects as narrow as 1 mm on the surface of the tested steel plate.

Anoikis-related gene signatures predict prognosis of lung adenocarcinoma patients and reveal immune infiltration.

Background: Lung adenocarcinoma (LUAD), a type of lung cancer, is one of the most aggressive and deadly malignancies worldwide. Malignant tumor cells exhibit strong anti-anoikis properties to achieve distant metastasis through the circulatory system. However, more research is needed to understand how anoikis is involved in the progression, metastasis and especially the prognosis of LUAD. Methods: We obtained anoikis-related genes (ARGs) from two websites, Harmonizome and Genecards, and integrated them to select and model the genes associated with LUAD prognosis. In addition, we investigated differences in the immune cell microenvironment and pathways of enrichment analysis between subtypes. We finally constructed a nomogram based on ARGs and used decision curve analysis (DCA) to demonstrate that this model could help clinicians make clinical decisions. Results: Sixty-four differentially expressed genes (DEGs) were found to be associated with survival, and of these, six were chosen to build a prognostic model. The time-dependent receiver operating characteristic (ROC) curves showed that the model had a satisfactory predictive ability. Enrichment analysis and immune microenvironment analysis revealed that the immune status and drug sensitivity of populations at high and low risk were different. We integrated the clinicopathological features of LUAD with the risk score to build the nomogram. The nomogram was shown to be a good predictor of short- and long-term survival in LUAD patients through DCA analysis. Conclusions: This new model based on six ARGs and nomograms in our study could help patients with LUAD develop personalized treatment plans.

Diagnostic potential of [18F]FDG PET/MRI in non-small cell lung cancer lymph node metastasis: a meta-analysis.

PURPOSE: This meta-analysis evaluated the diagnostic accuracy and diagnostic value of [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC. METHODS: Relevant articles in PubMed, Embase, Web of Science, and the Cochrane Library were searched until January 2023. Research evaluating [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC was included. Pooled estimates of sensitivity, specificity, PLR, and NLR were calculated by the "Stata" software. RESULTS: Nine researches were included, containing 618 patients. The pooled sensitivity of [18F]FDG PET/MRI for detecting mediastinal lymph node staging of NSCLC was 0.82 (0.70-0.90), and the pooled specificity was 0.88 (0.82-0.93). PLR and NLR were 7.38 (4.73-11.52) and 0.20 (0.11-0.36), respectively. The AUC value of this imaging modality was 0.92 (0.90-0.94). The post-test probability for [18F]FDG PET/MRI might rise to 88% when the pre-test probability was set at 50%. CONCLUSIONS: We considered [18F]FDG PET/MRI as an effective imaging tool with relatively high specificity and sensitivity. It has great potential to be used in the clinical management of patients in NSCLC who are amenable to early surgery. More studies with large sample sizes in the same direction are needed in future to obtain more reliable evidence-based support.

Head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis staging in non-small cell lung cancer: a meta-analysis.

PURPOSE: The current meta-analysis aimed to compare the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with 18F-FDG PET/magnetic resonance imaging (MRI) in non-small cell lung cancer (NSCLC) lymph node metastasis staging. METHODS: We searched the PubMed, Web of Science, and Embase databases for relevant articles between November 1992 and September 2022. Studies evaluating the head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis in patients with NSCLC were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Performance Studies-2 tool. RESULTS: The analysis includes six studies with a total of 434 patients. The pooled sensitivity of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.78 [95% confidence interval (CI): 0.59-0.90] and 0.84 (95% CI: 0.68-0.93), and the pooled specificity was 0.87 (95% CI: 0.72-0.94) and 0.87 (95% CI: 0.80-0.92), respectively. The accuracy of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.81 (95% CI: 0.71-0.90) and 0.84 (95% CI: 0.75-0.92), respectively. When the pre-test probability was set at 50%, the post-test probability for 18F-FDG PET/CT could increase to 85%, and the post-test probability for 18F-FDG PET/MRI could increase to 87%. CONCLUSION: 18F-FDG PET/CT and 18F-FDG PET/MRI have similar diagnostic performance in detecting lymph node metastasis in NSCLC. However, the results of this study were from a small sample study, and further studies with larger sample sizes are needed.

Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Store-operated Ca2+ channels blockers inhibit lipopolysaccharide induced astrocyte activation.

The destruction of calcium homeostasis is an important factor leading to neurological diseases. Store-operated Ca(2+) (SOC) channels are essential for Ca(2+) homeostasis in many cell types. However, whether SOC channels are involved in astrocyte activation induced by lipopolysaccharide (LPS) still remains unknown. In this study, we used LPS as an exogenous stimulation to investigate the role of SOC channels in astrocyte activation. Using calcium imaging technology, we first found that SOC channels blockers, 1-[h-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) and 2-aminoethyldiphenyl borate (2-APB), inhibited LPS induced [Ca(2+)]i increase, which prompted us to speculate that SOC channels may be involved in LPS induced astrocyte activation. Further experiments confirmed our speculation shown as SOC channels blockers inhibited LPS induced astrocyte activation characterized as cell proliferation by MTS and BrdU assay, raise in glial fibrillary acidic protein expression by immunofluorescence and Western Blot and secretion of interleukin 6 (IL-6) and interleukin 1ß (IL-1ß) by ELISA. So, our studies showed that SOC channels are involved in LPS-induced astrocyte activation.

The complete genomic sequence of a novel mycovirus from Rhizoctonia solani AG-1 IA strain B275.

The complete genome of a novel mycovirus, Rhizoctonia solani dsRNA virus 1 (RsRV1) was sequenced and analyzed. It is composed of two dsRNA genome segments, 2379 bp and 1811 bp in length, which were referred to as RsRV1-1 and RsRV1-2, respectively. RsRV1-1 contains a single open reading frame (ORF1), which has a conserved RNA-dependent RNA polymerase (RdRp) domain, whereas RsRV1-2 contains a single ORF2, which might encode a multifunctional protein. The genome organization of RsRV1 is similar to that of members of the family Partitiviridae. However, phylogenetic analysis indicated that RsRV1 formed a distinct clade together with three other unclassified viruses, suggesting that RsRV1 may belong to a new family of dsRNA mycoviruses. This is the first report of the full-length nucleotide sequence of a novel dsRNA mycovirus, RsRV1, infecting R. solani AG-1 IA strain B275, the causal agent of rice sheath blight.

FRAM-based causal analysis and barrier measures to mitigate dust explosions: A case study.

Both the number of dust explosion accidents and the resulting number of casualties have increased dramatically in recent years. To reduce this risk of dust explosions, we use the functional resonance analysis method (FRAM) to analyze the cause of the dust explosion accident at the Kunshan factory and propose barrier measures to prevent such accidents. The functional units that changed in the production system during the accident and how these functional units coupled to eventually cause the dust explosion were examined and explained. In addition, barrier measures were developed for functional units that changed during production and emergency systems defined to block the propagation of changes between functions and prevent resonance. Through case study, the identification of key functional parameters in both triggering the initial explosion and in then allowing its spread are key to define barriers to prevent a recurrence of such an event. FRAM uses system function coupling instead of traditional linear causality to explain the accident process, and develops barrier measures for changing function units, providing a novel thinking strategy and method for the analysis of accidents and their prevention.

Effects of waterlogging at different growth stages on the photosynthetic characteristics and grain yield of sorghum (Sorghum bicolor L.).

Various plants, including sorghum (Sorghum bicolor L.), are exposed to waterlogging; however, little is known about the effects of waterlogging at different growth stages on sorghum. A pot experiment was conducted using two sorghum hybrids, Jinuoliang 01 (JN01) and Jinza 31 (JZ31), to investigate the effects of waterlogging at different growth stages on the photosynthesis enzyme activity, chlorophyll content, malondialdehyde (MDA) content, photosynthetic parameters, dry matter accumulation, and grain yield. The experiment was conducted using waterlogging treatments implemented at the five-leaf stage (T1), flowering stage (T2), and filling stage (T3), using standard management (no waterlogging) as a control (CK). The adverse effects of waterlogging on sorghum growth varied with the waterlogging timing, with the maximum impact at T1, followed by T2 and T3. JZ31 was more sensitive to waterlogging compared to JN01. Waterlogged conditions inhibited the photosynthetic enzyme activity and reduced the chlorophyll content and photosynthesis, ultimately lowering the biomass yield and grain yield. The maximum yield loss was observed with the T1 waterlogging treatment; the grain yield of JN01 and JZ31 decreased by 52.01-54.58% and 69.52-71.97%, respectively, compared with CK. Furthermore, the decline in grain yield in T1 was associated with reducing grain number per panicle. These findings indicate that sorghum is sensitive to waterlogging at the five-leaf stage and JZ31 is more sensitive to waterlogging than JN01, which may provide a basis for selecting genotypes and management measures to cope with waterlogging in sorghum.

Frequency of metastases within the hypothalamic-pituitary area and the associated high-risk factors in patients with brain metastases.

Objective: Brain radiotherapy often results in impairment of hypothalamic-pituitary (HT-P) function, which in turn causes secretory dysfunction of related hormones. In this paper, the frequency of metastasis in the HT-P area and its high-risk factors in patients with brain metastasis were retrospectively analyzed, and thus provide experimental evidence for protecting HT-P area during whole brain radiotherapy (WBRT). Methods: A retrospective analysis was performed on the data of patients with brain metastasis diagnosed by cranial magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The anatomical positions of the hypothalamus and pituitary were delineated, followed by their expansion by 5 mm outwards, respectively, in the three-dimensional direction, and the hypothalamus +5 mm and pituitary +5 mm were obtained as the avoidance area, in which the frequency of brain metastasis was evaluated. Univariate and multivariate logistic regression models were used to analyze the high risk factors of brain metastasis in HT-P area. Results: A total of 3,375 brain metastatic lesions from 411 patients were included in the analysis. The rates of brain metastasis in the hypothalamus +5 mm and pituitary +5 mm in the whole group of cases were 2.9% (12/411) and 1.5% (6/411) respectively; the frequency of lesions was 0.4% (13/3375) and 0.2% (6/3375) respectively. Univariate and multivariate analyses showed that the number of brain metastases (OR = 14.946; 95% CI = 4.071-54.880; p < 0.001), and the occurrence of brain metastasis in the pituitary (OR = 13.331; 95% CI = 1.511-117.620; p = 0.020) were related to brain metastasis in the hypothalamus, and that the only relevant factor for brain metastasis in the pituitary was the occurrence of that in the hypothalamus (OR = 0.069; 95% CI = 0.010-0.461; p = 0.006). There was no correlation between tumor pathological types, the maximum diameter, the total volume of brain metastatic lesions and the risk of brain metastasis in hypothalamus and pituitary. Conclusion: The frequency of brain metastasis in the HT-P area is extremely low. The risk of brain metastases in the hypothalamus is correlated with their number. The larger the number of metastatic lesions, the higher the frequency of brain metastasis. Protection of the HT-P area during WBRT may be unlikely to compromise the tumor recurrence rate for patients with a relatively small number of brain metastases.

Clinical analysis of tubular stapler-assisted nested anastomosis in the prevention of postoperative esophageal cancer complications.

Background: Esophageal cancer (EC) is one of the most common malignant tumor types. Surgery is considered the treatment of choice for patients with early- and mid-stage EC. However, because of the traumatic nature of EC surgery and the need for gastrointestinal reconstruction, high rates of postoperative complications such as anastomotic leakage or stenosis, esophageal reflux, and pulmonary infection exist. Its time to explore a novel esophagogastric anastomosis method for McKeown EC surgery to reduce the postoperative complication. Methods: This study recruited a total of 544 patients who underwent McKeown resection for EC between January 2017 and August 2020. The tubular stapler-assisted nested anastomosis was taken as the time node, including 212 patients in the traditional tubular mechanical anastomosis group and 332 patients in the tubular stapler-assisted nested anastomosis group. The 6-month postoperative incidence of anastomotic fistula and anastomotic stenosis was recorded. Anastomosis in McKeown operation for EC and the influence of different anastomosis methods on clinical efficacy were investigated. Results: Compared with traditional mechanical anastomosis, tubular stapler-assisted nested anastomosis had a lower incidence of anastomotic fistula (0% vs. 5.2%), lung infection (3.3% vs. 11.8%), gastroesophageal reflux (6.9% vs. 16.0%), anastomotic stenosis (3.0% vs. 10.4%), neck incision infection (0.9% vs. 7.1%), anastomositis (16.6% vs. 23.6%), and a shorter surgical duration (11.02±1.54 vs. 18.53±3.20 min). Statistical significance was indicated at P<0.05. No significant difference was detected in the incidence of arrhythmia, recurrent laryngeal nerve injury, or chylothorax between the 2 groups. Due to its good effect in McKeown surgery for EC, stapler-assisted nested anastomosis has been widely used in McKeown surgery for EC, and has become a common anastomosis method in our department for McKeown surgery for EC. However, large sample-sized studies and long-term efficacy observation are still needed. Conclusions: The use of tubular stapler-assisted nested anastomosis can significantly reduce the incidence of complications such as anastomotic fistula, anastomotic stricture, gastroesophageal reflux, and pulmonary infection; therefore, it constitutes the preferred technique for cervical anastomosis in McKeown esophagogastrectomy.

O-GlcNAc transferase in astrocytes modulates depression-related stress susceptibility through glutamatergic synaptic transmission.

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte-specific knockout preserved the neuronal morphology atrophy and Ca2+ activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants.

Effect of nucleos(t)ide analogues on blood lipid profiles in patients with chronic hepatitis B: A cross-sectional survey.

This study aimed to explore the effects of the 3 nucleos(t)ide analogues (NAs) on lipid levels. We retrospectively included patients treated with NAs at 2 centers and collected their clinical data at their visiting points. Differences in blood lipid levels were analyzed by statistical methods, and factors related to hyperlipidemia were discussed. In these 2 centers, the prevalence rates of hypercholesterolemia were 12/181 (6.6%) for tenofovir alafenamide fumarate (TAF)-, 0/158 (0%) for tenofovir disoproxil fumarate (TDF)-, and 13/182 (7.1%) for entecavir (ETV)-treated individuals (P = .003). The prevalence rates of hypertriglyceridemia were 30/181 (16.6%) for TAF-, 11/158 (7.0%) for TDF-, and 26/182 (14.3%) for ETV-treated individuals (P = .025). In TAF (n = 181, 10 [6, 15] months), TDF (n = 158, 18 [7.5, 45] months), and ETV (n = 182, 24 [10, 60] months) groups, total cholesterol (TC) levels were 4.63 ±â€…0.91 mmol/L, 3.86 ±â€…0.61 mmol/L, and 4.53 ±â€…0.87 mmol/L, respectively; triglyceride (TG) levels were 1.27 ±â€…0.76 mmol/L, 0.87 ±â€…0.51 mmol/L, and 1.14 ±â€…0.67 mmol/L, respectively (P < .001). In multivariate regression analysis, factors associated with hypercholesterolemia were age (adjusted hazard risk [HR] = 1.055 [1.018-1.094]; P = .003) and body mass index (BMI) (adjusted HR = 0.817 [0.669-0.998]; P = .048). Factors associated with hypertriglyceridemia were TAF group (vs. TDF group) (adjusted HR = 0.405 [0.167-0.980]; P = .045), age (adjusted HR = 1.028 [1.002-1.055]; P = .038), and sex (adjusted HR = 0.190 [0.079-0.456]; P < .001). Among the patients treated with TAF (10 [6, 15] months), TDF (18 [7.5, 45] months), and ETV (24 [10, 60] months), the blood lipid levels in the TDF group were lower than those in the TAF group and ETV group, and the occurrence of hyperlipidemia was associated with age, sex, BMI, and different treatment.

LysM-positive neurons drive Tuberous Sclerosis Complex (TSC)-associated brain lesions.

Mutations of Tsc1 or Tsc2 can lead to excessive activation of mTORC1 and cause Tuberous Sclerosis Complex (TSC), which is an autosomal dominant genetic disease prominently characterized by seizures, mental retardation and multiorgan hamartoma. In TSC, pathological changes in the central nervous system are the leading cause of death and disability. In decades, series of rodent models have been established by mutating Tsc1 or Tsc2 genes in diverse neural cell lineages to investigate the underlying cellular and molecular mechanisms, however, the cellular origin triggering neural pathological changes in TSC is undetermined. In this study, we generated a novel mouse model involving conditional deletion of Tsc1 in lysozyme 2 (Lyz2)-positive cells which replicated several features of brain lesions including epileptic seizures, megalencephaly, highly enlarged pS6-positive neurons and astrogliosis. In addition, we confirmed that bone marrow-derived myeloid cells including microglia with Tsc1 deficiency are not the decisive lineage in the cerebral pathologies in TSC. These histological assays in our murine model indicate an essential contribution of Lyz2-positive neurons to TSC progression. The Lyz2-positive neural population-specific onset of Tsc1 loss in murine postnatal brain might be the key to pathological phenotypes. Our findings thus provided evidences supporting new insights into the role of Lyz2-positive neurons in TSC events.