DIEANet: an attention model for histopathological image grading of lung adenocarcinoma based on dimensional information embedding.

Efficient and rapid auxiliary diagnosis of different grades of lung adenocarcinoma is conducive to helping doctors accelerate individualized diagnosis and treatment processes, thus improving patient prognosis. Currently, there is often a problem of large intra-class differences and small inter-class differences between pathological images of lung adenocarcinoma tissues under different grades. If attention mechanisms such as Coordinate Attention (CA) are directly used for lung adenocarcinoma grading tasks, it is prone to excessive compression of feature information and overlooking the issue of information dependency within the same dimension. Therefore, we propose a Dimension Information Embedding Attention Network (DIEANet) for the task of lung adenocarcinoma grading. Specifically, we combine different pooling methods to automatically select local regions of key growth patterns such as lung adenocarcinoma cells, enhancing the model's focus on local information. Additionally, we employ an interactive fusion approach to concentrate feature information within the same dimension and across dimensions, thereby improving model performance. Extensive experiments have shown that under the condition of maintaining equal computational expenses, the accuracy of DIEANet with ResNet34 as the backbone reaches 88.19%, with an AUC of 96.61%, MCC of 81.71%, and Kappa of 81.16%. Compared to seven other attention mechanisms, it achieves state-of-the-art objective metrics. Additionally, it aligns more closely with the visual attention of pathology experts under subjective visual assessment.

Identification of novel mammalian viruses in tree shrews ( Tupaia belangeri chinensis).

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Deciphering the In Situ Reconstruction of Metal Phosphide/Nitride Dual Heterostructures for Robust Alkaline Hydrogen Evolution Above 3 A cm-2.

Hydrogen evolution reaction (HER) in neutral or alkaline electrolytes is appealing for sustainable hydrogen production driven by water splitting, but generally suffers from unsatisfied catalytic activities at high current densities owing to extra kinetic energy barriers required to generate protons through water dissociation. In response, here, a competitive Ni3 N/Co3 N/CoP electrocatalyst with multifunctional interfacial sites and multilevel interfaces, in which Ni3 N/CoP performs as active sites to boost initial water dissociation and Co3 N/CoP accelerates subsequent hydrogen adsorption process as confirmed by density functional theory calculations and in situ X-ray photoelectron spectroscopy analysis, is reported. This hybrid catalyst possesses extraordinary HER activity in base, featured by extremely low overpotentials of 115 and 142 mV to afford 500 and 1000 mA cm-2 , respectively, outperforming most ever-reported metal phosphides-based catalysts. This catalyst presents an ultrahigh current density of 3545 mA cm-2 by a factor of 4.96 relative to noble Pt/C catalysts (715 mA cm-2 ) at 0.2 V. Assembled with Fe(PO3 )2 /Ni2 P anode, industrial-level current densities of 500/1000 mA cm-2 at ultralow cell voltages of 1.62/1.66 V for overall water electrolysis with outstanding long-term stability are actualized. More interestingly, this hybrid catalyst also performs well in acidic, neutral freshwater, and seawater requiring relatively low overpotentials of 140, 290, and 331 mV to reach 500 mA cm-2 . Particularly, this catalyst can withstand electrochemical corrosion without obvious activity decay at the industrial-level current densities for over 100 h in base. This work provides a cornerstone for the construction of advanced catalysts operated in different pH environments.

Fangji Huangqi decoction ameliorates membranous nephropathy through the upregulation of BNIP3-mediated mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FJHQ), a traditional Chinese medicinal formula outlined in Zhang Zhongjing's "Jin Gui Yao Lue" during the Han Dynasty, is often used to treat conditions characterized by symptoms like edema and dysuria, including membranous nephropathy (MN). Despite its proven clinical effectiveness, the exact mechanisms through which FJHQ acts on MN remain elusive. AIM OF THE STUDY: This study aimed to investigate whether FJHQ enhances BNIP3-mediated mitophagy in podocytes by promoting BNIP3 expression and whether this improvement leads to the amelioration of MN. MATERIALS AND METHODS: In this study, by establishing passive Heymann nephritis (PHN) rats, an experimental rat model of MN induced by sheep anti-rat Fx1A serum, we evaluated the effects of FJHQ in vivo. In vitro experiments were carried out by treating primary podocytes with experimental rat serum. Furthermore, the potential mechanism by which FJHQ acts through BNIP3 was further examined by transfecting primary podocytes with the siRNA of BNIP3 or the corresponding control vector. RESULTS: After 4 weeks, significant kidney damage was observed in the rats in the model group, comparatively, FJHQ markedly decreased urine volume, 24-h urinary protein, blood urea nitrogen (BUN), creatinine (Scr), and increased serum total albumin (ALB). Histology showed that FJHQ caused significant improvements in glomerular hyperplasia, and IgG immune complex deposition in MN rats. JC-1 fluorescence labelling and flow cytometry analysis showed that FJHQ could significantly increase mitochondrial membrane potential in vivo. In the mitochondria of MN model rats, FJHQ was able to down-regulate the expression of P62 and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I, according to Western blot and immunofluorescence studies. Furthermore, FJHQ has been shown to significantly up-regulate mitochondrial membrane potential, down-regulate P62 expression in mitochondria, and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I in mitochondria at the cellular level. After the administration of the autophagy inhibitor chloroquine, the serum of rats treated with FJHQ further increased the expression of LC3 II/LC3 I in primary podocytes, showing higher autophagy flow. After the interference of BNIP3 in podocytes, the effect of FJHQ on mitochondrial membrane potential and autophagy-related proteins almost disappeared. CONCLUSION: FJHQ enhanced mitophagy in podocytes by promoting the expression of BNIP3, thereby contributing to the amelioration of MN. This work reveals the possible underlying mechanism by which FJHQ improves MN and provides a new avenue for MN treatment.

Characteristics of inhibitory active substances produced by Pseudoalteromonas SW-1.

To confirm the antagonistic activity characterization of the strain Pseudoalteromonas SW-1 (P. SW-1), its cell-free supernatant (CFS) was studied against a clam pathogenic strain of Vibrio Alginolyticu MP-1 (V.MP-1). The CFS of P. SW-1 exhibited evident antagonistic activities against the pathogens, and the absorbance value (600 nm) of V. MP-1 remained at a lower level at 24 h when compared with the control. The results showed that the inhibitory activities of strain P. SW-1 CFS showed differences after treatment with heat, acid and alkali, and proteinase K. The CFS of P. SW-1 inhibitory activities decreased after treatment with heat, but the inhibitory activities of strain P. SW-1 CFS were still effective after treatment with proteinase K for 24 h. The acid and alkali treatments could increase the inhibitory activities of strain P. SW-1 CFS. Therefore, the ammonium sulfate precipitation test also indicated that P. SW-1 could produce some active protein compounds to antagonize pathogenic V. MP-1.

Visible Light Motivated the Photocatalytic Degradation of P-Nitrophenol by Ca2+-Doped AgInS2.

4-Nitrophenol (4-NP) is considered a priority organic pollutant with high toxicity. Many authors have been committed to developing efficient, green, and environmentally friendly technological processes to treat wastewater containing 4-NP. Here, we investigated how the addition of Ca2+ affects the catalytic degradation of 4-NP with AgInS2 when exposed to light. We synthesized AgInS2 (AIS) and Ca2+-doped AgInS2 (Ca-AIS) with varying amounts of Ca2+ using a low-temperature liquid phase method. The SEM, XRD, XPS, HRTEM, BET, PL, and UV-Vis DRS characteristics were employed to analyze the structure, morphology, and optical properties of the materials. The effects of different amounts of Ca2+ on the photocatalytic degradation of 4-NP were investigated. Under visible light illumination for a duration of 120 min, a degradation rate of 63.2% for 4-Nitrophenol (4-NP) was achieved. The results showed that doping with an appropriate amount of Ca2+ could improve the visible light catalytic activity of AIS. This work provides an idea for finding suitable cheap alkaline earth metal doping agents to replace precious metals for the improvement of photocatalytic activities.

Prognostic nomograms for breast cancer with lung metastasis: a SEER-based population study.

BACKGROUND: Lung metastasis is a significant adverse predictor of prognosis in patients with breast cancer. Accurate estimation for the prognosis of patients with lung metastasis and population-based validation for the models are lacking. In the present study, we aimed to establish the nomogram to identify prognostic factors correlated with lung metastases and evaluate individualized survival in patients with lung metastasis based on SEER (Surveillance, Epidemiology, and End Results) database. METHODS: We selected 1197 patients diagnosed with breast cancer with lung metastasis (BCLM) from the SEER database and randomly assigned them to the training group (n = 837) and the testing group (n = 360). Based on univariate and multivariate Cox regression analysis, we evaluated the effects of multiple variables on survival in the training group and constructed a nomogram to predict the 1-, 2-, and 3-year survival probability of patients. The nomogram were verified internally and externally by Concordance index (C-index), Net Reclassification (NRI), Integrated Discrimination Improvement (IDI), Decision Curve Analysis (DCA), and calibration plots. RESULTS: According to the results of multi-factor Cox regression analysis, age, histopathology, grade, marital status, bone metastasis, brain metastasis, liver metastasis, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), surgery, neoadjuvant therapy and chemotherapy were considered as independent prognostic factors for patients with BCLM. The C-index in the training group was 0.719 and the testing group was 0.695, respectively. The AUC values of the 1-, 2-, and 3-year prognostic nomogram in the training group were 0.798, 0.790 and 0.793, and the corresponding AUC values in the testing group were 0.765, 0.761 and 0.722. The calculation results of IDI and NRI were shown. The nomograms significantly improved the risk reclassification for 1-, 2-, and 3-year overall mortality prediction compared with the AJCC 7th staging system. According to the calibration plot, nomograms showed good consistency between predicted and actual overall survival (OS) values for the patients with BCLM. DCA showed that nomograms had better net benefits at different threshold probabilities at different time points compared with the AJCC 7th staging system. CONCLUSIONS: Nomograms that predicted 1-, 2-, and 3-year OS for patients with BCLM were successfully constructed and validated to help physicians in evaluating the high risk of mortality in breast cancer patients.

Trajectories of Fasting Plasma Glucose and Risks of Chronic Kidney Disease in a General Chinese Population: A Retrospective Study.

Aim: To investigate the association between longitudinal changing patterns of fasting plasma glucose (FPG), and kidney function change in the general population. Methods: We conducted a retrospective, longitudinal cohort study of a health examination center database in China. Subjects who had at least three visits from 2011 to 2018 with baseline eGFR ≥60 mL/min/1.73 m2 were enrolled. The FPG trajectories were identified by group-based trajectory modeling (GBTM). We examined the association of eGFR slopes and FPG trajectories by Cox analysis. Results: Totally, 8114 participants were identified. Three heterogeneous FBP trajectories were detected by GBTM as low-stable group (n=7294), moderate-stable group (n=657) and high-stable group (n=163). The high-stable group had lower baseline eGFR, a higher percentage of fast eGFR slope, lower HDL-c, higher LDL-c, higher cholesterol, and higher Lg(triglyceride). Cox analysis showed that the high-stable trajectory was a risk factor for fast eGFR decline (for eGFR slope <-4 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 1.544 [0.876, 2.722]; for eGFR slope <-5 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 2.117[1.100, 4.075]). Further, we analyzed a subgroup in which participants' long-term FPG was normal. We divided this subgroup into four trajectories by GBTM, and Cox analysis showed that after adjustment for other potential confounding factors, the high-stable trajectory was an independent risk factor for fast eGFR slope (for eGFR slope <-4 mL/min per 1.73 m2 per year, adjusted HR [95% CI] HR 1.640[1.050, 2.561]; for eGFR slope <-5 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 1.818[1.018, 3.248]) in subgroup. Conclusion: We found that discrete FPG trajectories were significantly associated with risk of fast eGFR slope in individuals and those with long-term normal FPG. These observations suggest the importance of early prevention of CKD among individuals who are high-glycemic and normoglycemic.

Characterization of long-term ex vivo expansion of tree shrew spermatogonial stem cells.

Tree shrews ( Tupaia belangeri chinensis) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based gene editing platform to generate transgenic tree shrews. However, the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear. Here, we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages. We found that SSCs lost spermatogenesis ability after long-term expansion (>50 passages), as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia (SPG)-derived spermatocytes or spermatids marking spermatogenesis. RNA sequencing (RNA-seq) analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers. Specifically, DNA damage response and repair genes (e.g., MRE11, SMC3, BLM, and GEN1) were down-regulated, whereas genes associated with mitochondrial function (e.g., NDUFA9, NDUFA8, NDUFA13, and NDUFB8) were up-regulated after expansion. The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells. Supplementation with nicotinamide adenine dinucleotide (NAD +) precursor nicotinamide riboside (NR) exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture. Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.

Cognitive Deficits and Alzheimer's Disease-Like Pathologies in the Aged Chinese Tree Shrew.

Alzheimer's disease (AD) is the most common chronic progressive neurodegenerative disease in the elderly. It has an increasing prevalence and a growing health burden. One of the limitations in studying AD is the lack of animal models that show features of Alzheimer's pathogenesis. The tree shrew has a much closer genetic affinity to primates than to rodents and has great potential to be used for research into aging and AD. In this study, we aimed to investigate whether tree shrews naturally develop cognitive impairment and major AD-like pathologies with increasing age. Pole-board and novel object recognition tests were used to assess the cognitive performance of adult (about 1 year old) and aged (6 years old or older) tree shrews. The main AD-like pathologies were assessed by Western blotting, immunohistochemical staining, immunofluorescence staining, and Nissl staining. Our results showed that the aged tree shrews developed an impaired cognitive performance compared to the adult tree shrews. Moreover, the aged tree shrews exhibited several age-related phenotypes that are associated with AD, including increased levels of amyloid-ß (Aß) accumulation and phosphorylated tau protein, synaptic and neuronal loss, and reactive gliosis in the cortex and the hippocampal tissues. Our study provides further evidence that the tree shrew is a promising model for the study of aging and AD.

ASA-BiSeNet: improved real-time approach for road lane semantic segmentation of low-light autonomous driving road scenes.

The solution to the problem of road environmental perception is one of the essential prerequisites to realizing the autonomous driving of intelligent vehicles, and road lane detection plays a crucial role in road environmental perception. However, road lane detection in complex road scenes is challenging due to poor illumination conditions, the occlusion of other objects, and the influence of unrelated road markings. It also hinders the commercial application of autonomous driving technology in various road scenes. In order to minimize the impact of illumination factors on road lane detection tasks, researchers use deep learning (DL) technology to enhance low-light images. In this study, road lane detection is regarded as an image segmentation problem, and road lane detection is studied based on the DL approach to meet the challenge of rapid environmental changes during driving. First, the Zero-DCE++ approach is used to enhance the video frame of the road scene under low-light conditions. Then, based on the bilateral segmentation network (BiSeNet) approach, the approach of associate self-attention with BiSeNet (ASA-BiSeNet) integrating two attention mechanisms is designed to improve the road lane detection ability. Finally, the ASA-BiSeNet approach is trained based on the self-made road lane dataset for the road lane detection task. At the same time, the approach based on the BiSeNet approach is compared with the ASA-BiSeNet approach. The experimental results show that the frames per second (FPS) of the ASA-BiSeNet approach is about 152.5 FPS, and its mean intersection over union is 71.39%, which can meet the requirements of real-time autonomous driving.

Single-cell RNA sequencing shows the immune cell landscape in the kidneys of patients with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is a leading pathological type of the adult primary nephrotic syndrome. Some patients develop end-stage renal disease due to poor response to treatment with steroid and immunosuppressive agents. In order to explore the molecular mechanism of IMN, we collected renal tissue samples from IMN patients and healthy controls and performed analysis by single-cell RNA sequencing (scRNA-seq). A total of 11 kidney cell clusters were identified, including multiple myeloid cell clusters, NK/T cell clusters, and B cell clusters. Most kidney parenchymal and immune cells were enriched in the regulation of immune response, inflammation, fibrosis and endoplasmic reticulum stress. The macrophage population in the IMN group showed a highly activated profile with up-regulated genes related to chemotaxis, inflammation, phagocytosis and fibrosis. CD8+ T cells continued to be cytotoxic in IMN; however, a transition to "inflammageing" GZMK+ CD8+ T cells was observed. The proportion of activated B cells in renal tissues of IMN patients was much higher than that of normal controls, indicating that B cells in IMN might be activated by constant antigenic stimulation. Moreover, the cell-cell interaction analysis revealed the potential communication between renal glomerular cells and immune cells in IMN. Overall, scRNA-seq was applied to IMN to unravel the characteristics of immune cells and elucidate possible underlying mechanisms involved in the pathogenesis of IMN.

Rethinking neutrophil extracellular traps.

Neutrophils are a major subset of leukocytes in human circulating blood. In some circumstances, neutrophils release neutrophil extracellular traps (NETs). lnitially, NETs were considered to have a strong antibacterial capacity. However, currently, NETs have been shown to have a pivotal impact on various diseases. Different stimulators induce the production of different types of NETs, and their biological functions and modes of clearance do not appear to be the same. In this review, we will discuss several important issues related to NETs in order to better understand the relationship between NETs and diseases, as well as how to utilize the characteristics of NETs for disease treatment.

Advancement in preoperative desensitization therapy for ABO incompatible kidney transplantation recipients.

ABO incompatibility has long been considered an absolute contraindication for kidney transplantation. However, with the increasing number of patients with ESRD in recent years, ABO-incompatible kidney transplantation (ABOi-KT) has expanded the types of donors by crossing the blood group barrier through preoperative desensitization therapy. At present, the desensitization protocols consist of removal of preexisting ABO blood group antibody titers and prevention of ABO blood group antibody return. Studies have suggested similar patient and graft survival among ABOi-KT and ABOc-KT recipients. In this review, we will summarize the effective desensitization regimens of ABOi-KT, aiming to explore effective ways to improve the success rate and the long-term survival rate of ABOi-KT recipients.

Effects of intraoperative esketamine addition on gastrointestinal function after benign gynaecological laparoscopic surgery: a double-blind, randomized controlled study.

BACKGROUND: Gastrointestinal hypokinesis can occur transiently after benign gynecologic surgery. Opioids cause the side effect of postoperative gastrointestinal hypokinesis, but an opioid-sparing anaesthetic protocol based on esketamine reduces intraoperative opioid consumption. Therefore, this study hypothesised that an opioid-sparing anaesthetic protocol based on esketamine would shorten the gastrointestinal function recovery time after benign gynaecological laparoscopic surgery. METHODS: This was a prospective randomized controlled double-blind study conducted in a single centre. All patients scheduled for elective benign laparoscopic gynaecological surgery at Xing'an Meng People's Hospital, Inner Mongolia Autonomous Region, from November 2021 to April 2022 were consecutively enrolled and randomly divided into the opioid-sparing anaesthesia group (Group OS) and the conventional anaesthesia group (Group C). Postoperative first exhaust time, feeding time and postoperative nausea and/or vomiting (PONV) were analyzed in both groups. RESULTS: A total of 71 patients were enrolled in this study, including 35 in Group OS and 36 in Group C. The general condition, operative time, type of surgery, intraoperative bleeding, intraoperative fluid volume and intraoperative urine volume were not statistically different between the two groups. Compared with Group C, significantly shorter first postoperative flatus time (11 [8, 14] h vs. 14 [11, 18], p = 0.003) and anaesthesia resuscitation time (7 [6, 9] h vs. 9 [7, 11] h, p = 0.013)were observed in the OS group. The incidence of PONV in Group OS was significantly lower compared with Group C (11.4% vs. 41.7%, p = 0.007). CONCLUSION: The esketamine-based opioid-sparing anaesthetic protocol can shorten the postoperative first flatus time after benign laparoscopic surgery in gynaecology, and reduce the incidence of PONV. In addition, the application of esketamine may reduce the postoperative opioid dose requirement of patients. TRIAL REGISTRATION: This study was registered with the China Clinical Trials Registry (registration number: ChiCTR2100052528, 30/10/2021).

Driver identification and fatigue detection algorithm based on deep learning.

In order to avoid traffic accidents caused by driver fatigue, smoking and talking on the phone, it is necessary to design an effective fatigue detection algorithm. Firstly, this paper studies the detection algorithms of driver fatigue at home and abroad, and analyzes the advantages and disadvantages of the existing algorithms. Secondly, a face recognition module is introduced to crop and align the acquired faces and input them into the Facenet network model for feature extraction, thus completing the identification of drivers. Thirdly, a new driver fatigue detection algorithm based on deep learning is designed based on Single Shot MultiBox Detector (SSD) algorithm, and the additional layer network structure of SSD is redesigned by using the idea of reverse residual. By adding the detection of drivers' smoking and making phone calls, adjusting the size and number of prior boxes of SSD algorithm, improving FPN network and SE network, the identification and verification of drivers can be realized. The experimental results showed that the number of parameters decreased from 96.62 MB to 18.24 MB. The average accuracy rate increased from 89.88% to 95.69%. The projected number of frames per second increased from 51.69 to 71.86. When the confidence threshold was set to 0.5, the recall rate of closed eyes increased from 46.69% to 65.87%, that of yawning increased from 59.72% to 82.72%, and that of smoking increased from 65.87% to 83.09%. These results show that the improved network model has better feature extraction ability for small targets.

Coupling effect of critical properties shift and capillary pressure on confined fluids: A simulation study in tight reservoirs.

Critical properties shift and large capillary pressure are important contributors for the phase behavior altering of nanopore fluid. However, the effects of critical properties shift and large capillary pressure on the phase behavior are ignored in traditional compositional simulators, leading to inaccurate evaluation results of tight reservoirs. In this study, phase behavior and production of confined fluid in nanopores are studied. First, we developed a method for coupling the effect of critical properties shift and capillary pressure into the vapor-liquid equilibrium calculation base on Peng-Robinson equation of state. Second, a novel fully compositional numerical simulation algorithm considering effect of critical properties shift and capillary pressure on phase behavior is accomplished. Third, we have discussed the alterations of critical properties shift effect, capillary pressure effect and coupling effect on the composition of oil and gas production in detail. The critical properties shift and capillary pressure effects on oil and gas production in tight reservoirs are analyzed quantitatively through four cases, and the influences of the two effects in oil/gas production are compared. Based on the fully compositional numerical simulation, the simulator can rigorously simulate the impacts of component changes during production. The simulation results show that both the critical properties shift effect and the capillary pressure effect reduce the bubble point pressure of Changqing shale oil, and the influence are more prevalent in pores of smaller radius. In pores is larger than 50 nm, the phase behavior altering of the fluid can be ignored. In addition, we devised four cases to comprehensively investigate the effects of critical properties shift and large capillary pressure on production performance of tight reservoirs. The comparisons between the four cases show that the capillary pressure effect impacts the reservoir production performances greater than the critical properties shift effect, such as higher oil production, higher GOR, and lower content of lighter component and higher content of heavier component in the residual oil/gas. The results of coupling effects indicate that the critical properties shift effect would suppress the effect of the capillary pressure effect. In particular, the difference between the simulation results of the coupling effects and the base case is smaller than that between the simulation results of the capillary pressure effect and the base case.

Sirtuin 1 activator alleviated lethal inflammatory injury via promotion of autophagic degradation of pyruvate kinase M2.

Upregulation of pyruvate kinase M2 (PKM2) is critical for the orchestration of metabolism and inflammation in critical illness, while autophagic degradation is a recently revealed mechanism that counter-regulates PKM2. Accumulating evidence suggests that sirtuin 1 (SIRT1) function as a crucial regulator in autophagy. The present study investigated whether SIRT1 activator would downregulate PKM2 in lethal endotoxemia via promotion of its autophagic degradation. The results indicated that lethal dose of lipopolysaccharide (LPS) exposure decreased the level of SIRT1. Treatment with SRT2104, a SIRT1 activator, reversed LPS-induced downregulation of LC3B-II and upregulation of p62, which was associated with reduced level of PKM2. Activation of autophagy by rapamycin also resulted in reduction of PKM2. The decline of PKM2 in SRT2104-treated mice was accompanied with compromised inflammatory response, alleviated lung injury, suppressed elevation of blood urea nitrogen (BUN) and brain natriuretic peptide (BNP), and improved survival of the experimental animals. In addition, co-administration of 3-methyladenine, an autophagy inhibitor, or Bafilomycin A1, a lysosome inhibitor, abolished the suppressive effects of SRT2104 on PKM2 abundance, inflammatory response and multiple organ injury. Therefore, promotion of autophagic degradation of PKM2 might be a novel mechanism underlying the anti-inflammatory benefits of SIRT1 activator.

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Geographical traceability of gelatin in China using stable isotope ratio analysis.

Geographical traceability is crucial to the quality and safety control of gelatin. However, currently, methods for gelatin traceability have not been established anywhere in the world. This study aimed to investigate the possibility of differentiating the geographical origins of gelatin from different regions in China using stable isotope technology. To achieve this objective, 47 bovine stick bone samples from three different regions (Inner Mongolia, Shandong, and Guangxi, respectively) in China were collected, and gelatin was extracted from these bones using the enzymatic method. The fingerprint characteristics of stable isotopes of δ13C, δ15N, and δ2H of gelatin from different regions in China were studied. Moreover, isotopic changes from the bone to gelatin during the processing were examined to evaluate the effectiveness of these factors as origin indicators. The results of the one-way analysis of variance (ANOVA) showed that the δ13C, δ15N, and δ2H of gelatin from different regions display significant differences, and using the linear discriminant analysis (LDA), the correct differentiation of origin reached 97.9%. Certain differences in stable isotope ratios were observed during the processing of bone to gelatin samples. Nonetheless, the fractionation effect caused by the processing of bone to gelatin samples was not sufficient to influence the identification of gelatin from different origins, which proves that δ13C, δ15N, and δ2H are effective origin indicators of gelatin. In conclusion, the stable isotope ratio analysis combined with the chemometric analysis can be used as a reliable tool for identifying gelatin traceability.