Search

Electrical discharge machining (EDM) is one of the important machining processes to produce mold components. When using the EDM process, surface quality, processing time, accuracy, and electrode cost must be considered. The electrode wear is the main factor that causes error on the geometric accuracy, especially the workpiece corner. Therefore, this study proposes a novel electrode design to improve the geometric accuracy for the EDM process. Firstly, the effect of discharge current, electrode diameter, and depth of cut on the electrode wear and workpiece corner were investigated. Multiple regression and analysis of variant were used to analyze the experiment data. The electrode end-face design with compensation rule and algorithm was established based on the data analysis and error value. Furthermore, a compensated electrode end-face design system with human machine interface, which has a procedure guiding function, was developed. The system can design the electrode end-face for minimizing workpiece corner error and improve geometric accuracy. Finally, cutting experiments were conducted to verify the proposed method, and the results show that the proposed method can effectively enhance the geometric accuracy by around 22~37%.

A universal method to solve the differential equations of light-like geodesics is developed. The validity of this method depends on a new theorem, which is introduced for light-like geodesics in analogy to Beltrami's "geometrical" method for time-like geodesics. we apply the method to the Schwarzschild and Kerr spacetime as two examples. The general solutions of the light-like geodesic equations in the two spacetimes are derived straightforwadly. After setting $\theta=\pi/2$, the general light-like geodesics in Schwarzschild spacetime reduce to the same expression as that in literatures. The method developed and results obtained in this paper may be useful in modeling dynamical phenomena in strong gravitaional fields like black holes since the solutions are expressed in terms of elliptic integrals, which can be calculated effectively., Comment: 12 pages

Pseudorabies virus (PRV), an etiological agent of pseudorabies in livestock, has negatively affected the porcine industry all over the world. Epithelial cells are reported as the first site of PRV infection. However, the role of host proteins and its related signaling pathways in PRV replication is largely unclear. In this study, we performed a quantitative phosphoproteomics screening on PRV-infected porcine kidney (PK-15) epithelial cells. Totally 5723 phosphopeptides, corresponding to 2180 proteins, were obtained, and the phosphorylated states of 810 proteins were significantly different in PRV-infected cells compared with mock-infected cells (P ​ ​0.05). GO and KEGG analysis revealed that these differentially expressed phosphorylated proteins were predominantly related to RNA transport and MAPK signaling pathways. Further functional studies of NF-κB, transcription activator factor-2 (ATF2), MAX and SOS genes in MAPK signaling pathway were analyzed using RNA interference (RNAi) knockdown. It showed that only ATF2-knockdown reduces both PRV titer and viral genome copy number. JNK pathway inhibition and CRISPR/Cas9 gene knockout showed that ATF2 was required for the effective replication of PRV, especially during the biogenesis of viral genome DNA. Subsequently, by overexpression of the ATF2 gene and point mutation of the amino acid positions 69/71 of ATF2, it was further demonstrated that the phosphorylation of ATF2 promoted PRV replication. These findings suggest that ATF2 may provide potential therapeutic target for inhibiting PRV infection.

Purpose: To investigate the relationship between the corneal material stiffness parameter stress-strain index (SSI) and axial length (AL) elongation with varying severities of myopia, based on a mathematical estimation model.Methods: This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery in the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. First, we performed and tested an estimated AL model (ALMorgan) based on the mathematical equation proposed by Morgan. Second, we proposed an axial increment model (ΔAL) corresponding to spherical equivalent error (SER) based on ALemmetropia (ALMorgan at SER = 0) and subject’s real AL. Finally, we evaluated the variations of ΔAL with SSI changes based on the mathematical estimation model.Results: We found that AL was closely associated with ALMorgan (r = 0.91, t = 33.8, p < 0.001) with good consistency and SER was negatively associated with ΔAL (r = −0.89, t = −30.7, p < 0.001). The association of SSI with AL, ALemmetropia, and ΔAL can be summarized using the following equations: AL=27.7−2.04×SSI, ALemmetropia=23.2+0.561×SSI, and ΔAL=4.52−2.6×SSI. In adjusted models, SSI was negatively associated with AL (Model 1: β = −2.01, p < 0.001) and ΔAL (Model 3: β = −2.49, p < 0.001) but positively associated with ALemmetropia (Model 2: β = 0.48, p < 0.05). In addition, SSI was negatively associated with ΔAL among subjects with AL ≥ 26 mm (β = −1.36, p = 0.02).Conclusion: AL increased with decreasing SSI in myopia.

Southwestern China is the centre of diversity of Petrocosmea (Gesneriaceae). Here, a new species, named Petrocosmea dejiangensis, from north-eastern Guizhou, China, is described. The new species is most similar to P. martini, but it is distinguished from the latter by two dark blue-purple stripes inside the corolla tube along its entire length, the anthers shorter than the filaments, and the stigma apex rounded. Three populations comprising approximately 120 mature individuals were found at and near the type locality. This new taxon was assessed as “Data Deficient” (DD), according to IUCN standards.

BackgroundRibophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular homeostasis. Whether ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy (ERphagy) and mitophagy remains unclear. This study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte apoptosis.MethodsThe activity and regulation of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting, laser confocal microscopy and transmission electron microscopy. Then, we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic challenge.ResultsBoth cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy, which peaked at 24 h. When NUFIP1 was knocked down, T-lymphocyte apoptosis was noticeably increased. Conversely, the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte apoptosis. Consistently, the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type mice. In addition, the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway, and PERK–ATF4–CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of sepsis.ConclusionsNUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK–ATF4–CHOP pathway in the context of sepsis. Thus, targeting NUFIP1-mediated ribophagy might be of importance in reversing the immunosuppression associated with septic complications.

Cancer treatments always face challenging problems, particularly drug resistance due to tumor cell heterogeneity. The existing datasets include the relationship between gene expression and drug sensitivities; however, the majority are based on tissue-level studies. Study drugs at the single-cell level are perspective to overcome minimal residual disease caused by subclonal resistant cancer cells retained after initial curative therapy. Fortunately, machine learning techniques can help us understand how different types of cells respond to different cancer drugs from the perspective of single-cell gene expression. Good modeling using single-cell data and drug response information will not only improve machine learning for cell–drug outcome prediction but also facilitate the discovery of drugs for specific cancer subgroups and specific cancer treatments. In this paper, we review machine learning and deep learning approaches in drug research. By analyzing the application of these methods on cancer cell lines and single-cell data and comparing the technical gap between single-cell sequencing data analysis and single-cell drug sensitivity analysis, we hope to explore the trends and potential of drug research at the single-cell data level and provide more inspiration for drug research at the single-cell level. We anticipate that this review will stimulate the innovative use of machine learning methods to address new challenges in precision medicine more broadly.

Additional file 1: Fig. S1 Characteristics of the dataset and markers of cell subsets. Fig. S2 Trajectory and cell–cell interaction analyses of monocyte subtypes. Fig. S3 ScRNA-seq analysis reveals monocyte heterogeneity in septic patients with ARDS. Fig. S4 identification of splenic S100ahigh monocytes in murine sepsis. Fig. S5 S100A9 release of circulating and splenic monocytes upon septic challenge. Table S1 Clinical characteristics of enrolled patients. Table S2 Composition of clinical entities in each cluster.

This paper investigates the effects of Chongqing’s rural and urban residents and total resident population on economic development based on the residents’ consumption structure and analyses of economic development theories concerned by using the input-output table of Chongqing during 2002–2017 and SDA (Structure Decomposition Analysis) model. The study found that, compared with the previous years, the direct consumption of the primary industry’s unit output to the industrial products has decreased significantly in 2017, while the direct consumption to the tertiary industry has increased significantly; The direct consumption per unit output of the second industry is basically equal to that of the products of the industry, while the direct consumption of the products of the third industry has increased; The direct consumption per unit output value of the tertiary industry is basically equal to that of the primary industry. In the long run, the changes in consumption structure of rural and urban residents and total resident population and the increase in proportion of tertiary industry accelerate the transformation and upgrading of industrial structure. However, the effect of consumption structure on GDP (Gross Domestic Product) varies from year to year. On the whole, the changes of residents’ consumption have a positive effect on GDP (Gross Domestic Product).

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK–ATF4–CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03970-z.

Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-β (TGF-β)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.

Ferroptosis is a nonapoptotic form of programmed cell death triggered by the accumulation of reactive oxygen species (ROS) depended on iron overload. Although most investigations focus on the relationship between ferroptosis and cancer, neurodegenerative diseases, and ischemia/reperfusion injury, research on ferroptosis induced by immune-related inflammatory diseases, especially sepsis, is scarce. Sestrin2 (Sesn2), a highly evolutionary and stress-responsive protein, is critically involved in defense against oxidative stress challenges. Upregulated expression of Sesn2 has been observed in preliminary experiments to have an antioxidative function in the context of an inflammatory response. Nevertheless, the underlying function of Sesn2 in inflammation-mediated ferroptosis in the immune system remains uncertain. The current study aimed to demonstrate the protective effect of Sesn2 on ferroptosis and even correlations with ferroptosis and the functions of ferroptotic-dendritic cells (DCs) stimulated with lipopolysaccharide (LPS). The mechanism underlying DCs protection from LPS-induced ferroptosis by Sesn2 was further explored in this study. We found that the immune response of DCs assessed by co-stimulatory phenotypes was gradually enhanced at the peak time of 12 h upon 1 μg/ml LPS stimulation while ferroptosis in DCs treated with LPS at 24 h was significantly detected. LPS-induced ferroptosis showed a suppressive impact on DCs in phenotypic maturation, which was conversely relieved by the ferroptotic inhibitor. Compared with wild-type (WT) mice, DCs in genetic defective mice of Sesn2 (Sesn2−/−) exhibited exacerbated ferroptosis. Furthermore, the protective effect of Sesn2 on ferroptosis was noticed to be associated with the ATF4-CHOP-CHAC1 pathway, eventually exacerbating ferroptosis by degrading of glutathione. These results indicate that Sesn2 can suppress the ferroptosis of DCs in sepsis by downregulating the ATF4-CHOP-CHAC1 signaling pathway, and it might play an antioxidative role.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Glioma-associated macrophage/microglia (GAM) represents a key player in shaping a unique glioma ecosystem to facilitate tumor progression and therapeutic resistance. Numerous studies have been published concerning GAM, but no relevant bibliometric study has been performed yet. Our bibliometric study aimed to comprehensively summarize and analyze the global scientific output, research hotspots, and trendy topics of publications on GAM over time. Data on publications on GAM were collected using the Web of Science (WoS). The search date was 16 January 2022, and the publications were collected from 2002 to 2021. Totally, 1,224 articles and reviews were incorporated and analyzed in the current study. It showed that the annual publications concerning GAM kept increasing over the past 20 years. The United States had the largest number of publications and total citations. Holland, Kettenmann, and Gutmann were the top three authors in terms of citation frequency. Neuro-oncology represented the most influential journal in GAM studies, with the highest H-index, total citations, and publication numbers. The paper published by Hambardzumyan in 2016 had the highest local citations. Additionally, the analysis of keywords implied that “prognosis,” “tumor microenvironment,” and “immunotherapy” might become research hotspots. Furthermore, trendy topics in GAM studies suggested that “immune infiltration,” “immune microenvironment,” “bioinformatics,” “prognosis,” and “immunotherapy” deserved additional attention. In conclusion, this bibliometric study comprehensively analyzed the publication trend of GAM studies for the past 20 years, in which the research hotspots and trendy topics were also uncovered. This information offered scholars critical references for conducting in-depth studies on GAM in the future.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions. Thus, although their product ions could be acquired, their precursor ions are absent. Here, we present a new strategy, chromatographic retention behavior-SWATH (CRB-SWATH), that could unbiasedly capture poor-quality peaks and provide high resolutions of multiplexed mass spectroscopy (MS/MS) spectra in SWATH datasets. CRB-SWATH monitors CRBs of SWATH-MS signals under a series of altered elution gradients. As signals of compounds differ from noise by showing CRBs, both the precursor and fragment ions are captured, while ignoring their peak qualities. Moreover, CRB-SWATH offers good chances to resolve highly multiplexed MS/MS spectra in SWATH datasets because precursor ions coeluted in a single elution gradient often present different CRBs. In the untargeted metabolic analysis of Hela cell extracts, CRB-SWATH showed the advantage in exclusively capturing 2645 ions of poor-quality peaks (i.e., tiny peaks, discontinuous ion traces, tailing peaks, zigzag peaks, etc.), accounting for 34.4% of all the untargeted precursor ions extracted. Therein, it is noteworthy that among 2116 negative ions detected in hydrophilic interaction liquid chromatography (HILIC) mode, 1284 poor-quality ion peaks (>60%) were exclusively captured by CRB-SWATH. As CRB-SWATH automatically captures a large sum of true ion peaks of poor qualities, extracts MS/MS spectra of high purities, and provides chromatographic retention behaviors of untargeted metabolites for identification and classification, it could be a useful metabolomics tool for understanding biological phenomena better.

This study was performed to investigate the relationship between the aspartate transaminase and/or alanine transaminase ratio (DRR) and long-term mortality of patients diagnosed with sepsis or septic shock.We conducted a retrospective study among adult septic patients who were admitted to the surgical intensive care unit (ICU) of the Chinese People's Liberation Army (PLA) General Hospital from January 2014 to December 2018. Baseline characteristics were compared between survivors and non survivors. We performed univariate and multivariate Cox regression analyses to evaluate the relation of DRR with 180-day mortality. The potential prognostic value of DRR in predicting mortality rate was assessed by receiver operating characteristic (ROC) curve analysis. In addition, we conducted subgroup analysis by the optimal DRR cutoff value.We included a total of 183 patients in the current study, and 44 (24%) patients died within 180 days of hospitalization. Univariate and multivariate Cox analyses revealed that DRR was an independent predictor of 180-day mortality (hazard ratio [HR] 1.421, 95% confidence interval [CI] 1.073-1.883, P = 0.014). The predictive accuracy of DRR for 180-day mortality was presented as an ROC curve, which had an area under the curve (AUC) of 0.708 (95% CI 0.629-0.786, P0.001). After we stratified all enrolled patients into two groups by using the optimal cutoff value of 1.29, we observed a significantly higher mortality in patients with a relatively high DRR.An elevated DRR was associated with higher 180-day mortality among septic patients, and DRR might be an optimal marker for predicting the long-term mortality of sepsis. More prospective and randomized trials are needed to confirm the prognostic value of DRR.

The small intestine is located in the middle of the gastrointestinal tract, so small intestinal diseases are more difficult to diagnose than other gastrointestinal diseases. However, with the extensive application of artificial intelligence in the field of small intestinal diseases, with its efficient learning capacities and computational power, artificial intelligence plays an important role in the auxiliary diagnosis and prognosis prediction based on the capsule endoscopy and other examination methods, which improves the accuracy of diagnosis and prediction and reduces the workload of doctors. In this review, a comprehensive retrieval was performed on articles published up to October 2020 from PubMed and other databases. Thereby the application status of artificial intelligence in small intestinal diseases was systematically introduced, and the challenges and prospects in this field were also analyzed.

BackgroundSepsis is considered an intractable dysfunction that results from the disordered host immune response to uncontrolled infection. Even though the precise mechanism of sepsis remains unclear, scientific advances have highlighted the key role of various programmed cell death processes in the pathophysiology of sepsis. The current study aims to explore the worldwide research trend on programmed cell death in the setting of sepsis and assesses the achievements of publications from various countries, institutions, journals, and authors globally.Material and methodsAssociated publications during 2002–2022 with the topical subject of sepsis and programmed cell death were extracted from the Web of Science. VOSviewer was utilized to evaluate and map the published trend in the relevant fields.ResultsAll 2,037 relevant manuscripts with a total citation of 71,575 times were screened out by the end of 1 January 2022. China accounted for the largest number of publications (45.07%) and was accompanied by corporate citations (11,037) and H-index (48), which ranked second globally. The United States has been ranked first place with the highest citations (30,775) and H-index (88), despite a low publication number (29.95%), which was subsequent to China. The journal Shock accounted for the largest number of publications in this area. R. S. Hotchkiss, affiliated with Washington University, was considered to have published the most papers in the relevant fields (57) and achieved the highest citation frequencies (9,523). The primary keywords on the topic of programmed cell death in sepsis remarkably focused on “inflammation” “immunosuppression”, and “oxidative stress”, which were recognized as the core mechanisms of sepsis, eventually attributing to programmed cell death. The involved research on programmed cell death induced by immune dysregulation of sepsis was undoubtedly the hotspot in the pertinent areas.ConclusionsThe United States has been academically outstanding in sepsis-related research. There appears to be an incompatible performance between publications and quantity with China. Frontier advances may be consulted in the journal Shock. The leading-edge research on the scope of programmed cell death in sepsis should preferably focus on immune dissonance-related studies in the future.

Peptic ulcer (PU) is a common and frequently occurring disease. Although PU seriously threatens the lives and health of global residents, the applications of artificial intelligence (AI) have strongly promoted diversification and modernization in the diagnosis and treatment of PU. This minireview elaborates on the research progress of AI in the field of PU, from PU’s pathogenic factor Helicobacter pylori (Hp) infection, diagnosis and differential diagnosis, to its management and complications (bleeding, obstruction, perforation and canceration). Finally, the challenges and prospects of AI application in PU are prospected and expounded. With the in-depth understanding of modern medical technology, AI remains a promising option in the management of PU patients and plays a more indispensable role. How to realize the robustness, versatility and diversity of multifunctional AI systems in PU and conduct multicenter prospective clinical research as soon as possible are the top priorities in the future.

Background. Although serum calcium has been proven to be a predictor of mortality in a wide range of diseases, its prognostic value in critically ill patients with cardiogenic shock (CS) remains unknown. This retrospective observational study is aimed at investigating the association of admission calcium with mortality among CS patients. Methods. Critically ill patients diagnosed with CS in the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included in our study. The study endpoints included 30-day, 90-day, and 365-day all-cause mortalities. First, admission serum ionized calcium (iCa) and total calcium (tCa) levels were analyzed as continuous variables using restricted cubic spline Cox regression models to evaluate the possible nonlinear relationship between serum calcium and mortality. Second, patients with CS were assigned to four groups according to the quartiles (Q1-Q4) of serum iCa and tCa levels, respectively. In addition, multivariable Cox regression analyses were used to assess the independent association of the quartiles of iCa and tCa with clinical outcomes. Results. A total of 921 patients hospitalized with CS were enrolled in this study. A nonlinear relationship between serum calcium levels and 30-day mortality was observed (all P values for nonlinear trend < 0.001 ). Furthermore, multivariable Cox analysis showed that compared with the reference quartile (Q3: 1.11 ≤ iCa < 1.17 mmol / L ), the lowest serum iCa level quartile (Q1: iCa < 1.04 mmol / L ) was independently associated with an increased risk of 30-day mortality (Q1 vs. Q3: HR 1.35, 95% CI 1.00-1.83, P = 0.049 ), 90-day mortality (Q1 vs. Q3: HR 1.36, 95% CI 1.03-1.80, P = 0.030 ), and 365-day mortality (Q1 vs. Q3: HR 1.28, 95% CI 1.01-1.67, P = 0.046 ) in patients with CS. Conclusions. Lower serum iCa levels on admission were potential predictors of an increased risk of mortality in critically ill patients with CS.

Many viruses utilize molecular chaperone heat shock protein 90 (Hsp90) for protein folding and stabilization, however, the role of Hsp90 in herpesvirus lifecycle is obscure. Here, we provide evidence that Hsp90 participates in pseudorabies virus (PRV) replication. Viral growth kinetics assays show that Hsp90 inhibitor geldanamycin (GA) abrogates PRV replication at the post-penetration step. Transmission electron microscopy demonstrates that dysfunction of Hsp90 diminishes the quantity of PRV nucleocapsids. Overexpression and knockdown of Hsp90 suggest that de novo Hsp90 is involved in PRV replication. Mechanismly, dysfunction of Hsp90 inhibits PRV major capsid protein VP5 expression. Co-immunoprecipitation and indirect immunofluorescence assays indicate that Hsp90 interacts with VP5. Interestingly, Hsp70, a collaborator of Hsp90, also interacts with VP5, but doesn't affect PRV growth. Finally, inhibition of Hsp90 results in PRV VP5 degradation in a proteasome-dependent manner. Collectively, our data suggest that Hsp90 contributes to PRV virion assembly and replication via stabilization of VP5.

Sepsis represents a life-threatening organ dysfunction due to an aberrant host response. Of note is that majority of patients have experienced a severe immune depression during and after sepsis, which is significantly correlated with the occurrence of nosocomial infection and higher risk of in-hospital death. Nevertheless, the clinical sign of sepsis-induced immune paralysis remains highly indetectable and ambiguous. Given that, specific yet robust biomarkers for monitoring the immune functional status of septic patients are of prominent significance in clinical practice. In turn, the stratification of a subgroup of septic patients with an immunosuppressive state will greatly contribute to the implementation of personalized adjuvant immunotherapy. In this review, we comprehensively summarize the mechanism of sepsis-associated immunosuppression at the cellular level and highlight the recent advances in immune monitoring approaches targeting the functional status of both innate and adaptive immune responses.

This research proposes a method for auto-monitoring the air cutting condition of a machining process, so the air cutting time can be further improved to enhance the machining efficiency. A two-way data communication module with a CNC controller was established to achieve real-time monitoring and control function via TCP/IP protocol. The module enables the identification of the executing NC block and the cutting time during machining. The spindle load current and cutting vibration signals were used to on-line diagnose the cutting state (effective cutting or air cutting), and their associated NC codes were identified and recorded at the same time, based on the executing NC block in the CNC controller. An algorithm adopting this state change information to determine effective cutting time and air cutting time was developed and used to build an intelligent air cutting monitoring system, with a friendly human–machine interface. The system can detect air cutting time, effective cutting time, machine idle time, as well as the total machining time to improve the air cutting time to enhance the machining efficiency. Verification experiments were conducted, and the results showed the proposed method can accurately detect the air cutting occurrence and its associated NC blocks in the NC program.

Petrocosmea dejiangensis Sheng H.Tang & Jian Xu, sp. nov., Figure 1 Type:��� CHINA. Guizhou Province, Dejiang County, Nangan Town, at approximately 610 m elev., 28��22���12���N, 107��53���24���E [the voucher from plants cultivated at the Guizhou Botanical Garden, and collected in the locality presented on 12 May 2020], 3 May 2021, Sheng-Hu Tang 2021002 (holotype GZAC!). Petrocosmea dejiangensis has a highly fused upper lip. This important character is shared by 21 species of Petrocosmea. The new species is most similar to P. martini (Fig. 2) in the indumentum of the petiole, leaf blade, filaments, and ovary, but differs from it in having inconspicuous bracts (vs. conspicuous), two dark blue-purple stripes inside along the entire corolla tube (vs. two purple spots inside the tube under the filaments), throat blue-purple (vs. white), anthers shorter than filaments (vs. anthers subequal to filaments in length), and stigma apex rounded (vs. flat). Perennial herbs, stemless. Rhizome short, 3���4 mm long. Leaves all basal, 10 to 20; the inner leaves with petioles 0.5���1.5 cm long or absent, the outer leaves with petioles 3.5���6 cm long, petioles sparsely or densely descending pilose; leaf blades subcordate or suborbicular, 9.2���12.5 �� 9���12.2 mm, apex obtuse or rounded, base cordate, and margin crenate, papery when dry, both adaxial and abaxial blade surfaces densely pilose, ca. 0.5 mm long, lateral veins adaxially and abaxially inconspicuous, 2���3 on either side of the midrib. Cymes 1���9, one flower per cyme; peduncles 4.5���5.8 cm long, sparsely ascending pilose, and densely appressed pilose; bracts absent, rarely two, nearly opposite, inconspicuous, 0.3���0.5 mm long, sparsely pilose; pedicels 1.5���2.5 cm long, sparsely ascending pilose and densely appressed pilose. Calyx zygomorphic, densely erect pilose outside, glabrous inside; adaxial calyx lip 5.2���5.4 mm in length, 3-lobed nearly to the base, lobes 3.9���4.1 �� 1.1���1.2 mm, lanceolate, apex acuminate; abaxial calyx lip 2-lobed to the base, lobes 5���5.7 �� 1.3���1.5 mm, lanceolate, apex acuminate. Corolla blue-purple, 12.9���14.3 mm long, puberulent outside, glabrous inside; tube 4.1���4.4 mm long, broadly tubular, two dark blue-purple stripes extending inside along the entire corolla tube length; throat blue-purple, with two dark blue stripes; adaxial corolla lip 2.2���2.6 mm long, much shorter than abaxial corolla lip, indistinctly 2-lobed, apex emarginate, margin recurved; abaxial corolla lip 9���10 �� 11.7���12.8 mm, 3-lobed to the middle, lateral lobes obovate or ovate, 4.2���5.5 �� 4.1���4.3 mm, the middle one obovate or ovate, 4.5���5 �� 4.1���4.5 mm. Stamens two, included, adnate to the corolla tube near the base; filaments 3.5���4 mm long, densely glandular puberulent, curved near the middle; anthers ovate, ca. 2 �� 1.7 mm, dorsifixed, coherent at apex; parallel thecae, not confluent at apex, poricidal near the apex, sometimes dehiscing longitudinally from apex to above the middle. Staminodes three, included, adnate to the adaxial side of the corolla tube near the base, ca. 0.8 mm long, glabrous. Pistil 7.5���8.3 mm long; ovary densely appressed pilose, narrowly ovoid, 2���2.5 mm long, ca. 1.0 mm in diameter; style 5.5���5.8 mm long, 0.3 mm in diameter, glabrous; stigma nearly globose, ca. 0.35 mm in diameter, apex rounded. Capsules unknown. Phenology:��� Flowering occurs from April to May. Fruiting in the wild is unknown but likely occurs from September to October; only young fruits were observed. Etymology:��� The new taxon is named after the type locality, Dejiang County, China. Vernacular name:��� The Chinese name is ���D�� Ji&amacr;ng Sh�� H�� Di����� (���������M���). Distribution and habitat:��� Three populations with nearly 120 mature individuals were found at Nangan town, Dejiang County, Guizhou Province, China. The plants grew on moist shady rocks in valleys at an elevation of ca. 600��� 700 m. The main companion species were Platycarya strobilacea Siebold & Zuccarini (1843: 741���742), Lindera communis Hemsley (1891: 387), and Carpinus sp. Linnaeus (1753: 998) sp. Conservation status:��� Each time we visited the area, we discovered a new population. Three populations with approximately 120 mature individuals were found at and near the type locality. It is highly possible that more populations are present in the area. Until further investigation, the species should be designated as ���Data Deficient��� (DD) according to the IUCN standards (IUCN 2019). Morphological affinities:��� Although Petrocosmea dejiangensis and P. martini are similar in the shape of corolla, they differ in the morphology of bracts, color marks in the corolla, stamens, and the stigma. We have found three populations of P. dejiangensis at and near the type locality. The relatively smaller plant and leaf blades, the presence of two dark blue-purple stripes inside along the entire length of the corolla tube, anthers shorter than filaments, and stigma apex rounded were stable characters both in the wild and in the greenhouse. The detailed morphological comparison is shown in Table 1, as well as an identification key to the morphological alliance of P. dejiangensis. Additional specimens examined (paratype):��� CHINA. Guizhou Province: Dejiang County, Nangan Town, approximately 610 m, 29 August 2021 (young fruit), Jian Xu, Xuanze He & Shuo Yang DJ 20210829001 (GZAC!, CSH, IBK)., Published as part of Xu, Jian, Li, Sa, Tang, Sheng-Hu & Ren, Qi-Fei, 2022, Petrocosmea dejiangensis (Gesneriaceae), a new species from Guizhou, China, pp. 17-23 in Phytotaxa 539 (1) on pages 18-21, DOI: 10.11646/phytotaxa.539.1.2, http://zenodo.org/record/6345899, {"references":["Siebold, P. F. (B.) V. & Zuccarini, J. G. (1843) Platicaryn struhihicea Sieb, et Zuccur. Abhandlungen der Mathematisch-Physikalischen Klasse der Koniglich Bayerischen Akademie der Wissenschaften 3: 741 - 742.","Hemsley, W. B. (1891) Lindera communis Hemsl. The Journal of the Linnean Society, Botany 26: 387.","Linnaeus, C. (1753) Species Plantarum Vol. 2. Salvius, Stockholm, pp 561 - 1200.","IUCN (2019) Guidelines for using the IUCN Red List categories and criteria, Version 14. Prepared by the Standards and Petitions Committee. Available from: https: // www. iucnredlist. org / documents / RedListGuidelines. pdf (accessed 15 September 2021)."]}

BACKGROUND: Log odds of positive lymph nodes (LODDS) is a novel and promising ratio-based lymph node (LN) staging system in many malignancies. This study aimed to evaluate the prognostic value of LODDS, and comprehensively compare the prognostic predictive performance of LODDS with the American Joint Committee on Cancer (AJCC) N classification, number of positive lymph node (NPLN), and lymph node ratio (LNR) among node-positive lung squamous cell carcinoma (SCC) patients after surgery. METHODS: We identified 2,561 patients with N1/N2 stage SCC diagnosed between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. X-tile analysis was used to calculate the optimal cut-off value for each staging system. Univariable and Multivariable Cox regression analyses were used to assess the association of cancer-specific survival (CSS), and overall survival (OS) with N, NPLN, LNR, and LODDS, separately, and integrally. Moreover, linear trend χ(2) score, likelihood ratio (LR) test, Akaike information criterion (AIC), and Harrell concordance index (C-index) were adopted as criteria for assessing the predictive ability of each model. RESULTS: The optimal cut-off values for NPLN, LNR, and LODDS were 3, 0.28, and −0.37, respectively. N, NPLN, LNR, and LODDS were identified as independent prognostic predictors for CSS and OS in patients with SCC when each of them was incorporated into multivariable Cox model separately. Additionally, LODDS had the higher linear trend χ(2) score, higher LR χ(2) test score, lower AIC, and higher C-index compared to the other three systems. Moreover, a combination of N, NPLN, and LODDS was superior to any staging system alone for predicting prognosis. CONCLUSIONS: LODDS showed better predictive performance than N, NPLN, and LNR among patients with node-positive SCC after surgery. A combination of LODDS and the current AJCC TNM classification has the potential for becoming a better staging method to more precisely predicting prognosis.

Purpose The study was performed to estimate the diagnostic blood loss (DBL) volume during hospitalization and investigate its relationship with the development of moderate to severe hospital acquired anemia (HAA) and increased number of red blood cell (RBC) transfusion following extensive burns. Materials and methods This was a retrospective study of adult burned patients with total body surface area (TBSA) burn larger than 40%, who were admitted to burn center of Changhai hospital between January 2005 and December 2017. Results We included a final number of 157 patients in the present study. Moderate to severe HAA within the fourth week postburn was developed in 46 of 121 patients who stayed over 28-day hospitalization. Patients with moderate to severe HAA had both significantly higher total DBL volume [245 (IQR: 183.75, 325.25) mL vs 168 (119, 163) mL ; P = 0.001] and DBL volume per day [10.22 (IQR: 8.57, 12.38) mL vs 6.63 (5.22, 10.42) mL/day; P = 0.005]. Logistic regression analysis revealed that both DBL volume per day and TBSA burn were independent risk factors for the development of moderate to severe HAA. Conclusions Severely burned patients appear to be prone to develop HAA during hospitalization. The DBL volume contribute to the occurrence of moderate to severe HAA, which might be a modifiable target for preventing HAA.

ABO blood type has been reported to be a predictor of poor prognosis in critically ill patients. Here, we aim to correlate different blood types with clinical outcomes in patients with severe burns. We conducted a single-center retrospective cohort study by enrolling patients with severe burn injuries (≥40% TBSA) between January 2012 and December 2017. Baseline characteristics and clinical outcomes were compared between disparate ABO blood types (type O vs non-O type). Multivariate logistic and linear regression analyses were performed to identify an association between ABO blood type and clinical outcomes, including in-hospital mortality, the development of acute kidney injury (AKI), and hospital or ICU length of stay. A total of 141 patients were finally enrolled in the current study. Mortality was significantly higher in patients with type O blood compared with those of other blood types. The development of AKI was significantly higher in patients with blood type O vs non-O blood type (P = .001). Multivariate analysis demonstrated that blood type O was independently associated with in-hospital mortality and AKI occurrence after adjusting for other potential confounders. Our findings indicated the blood type O was an independent risk factor of both increased mortality and the development of AKI postburn. More prudent and specific treatments are required in treating these patients to avoid poor prognosis.

The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of great importance in maintaining the survival and function of cells and could be a potential therapeutic target for human diseases. Organelle-specific autophagy is one of the major subtypes of autophagy, selectively targeting different organelles for quality control. This type of autophagy includes mitophagy, pexophagy, reticulophagy (endoplasmic reticulum), ribophagy, lysophagy, and nucleophagy. These kinds of organelle-specific autophagy are reported to be beneficial for inflammatory disorders by eliminating damaged organelles and maintaining homeostasis. In this review, we summarized the recent findings and mechanisms covering different kinds of organelle-specific autophagy, as well as their involvement in various diseases, aiming to arouse concern about the significance of the quality control of multiple organelles in the treatment of inflammatory diseases. Abbreviations: ABCD3: ATP binding cassette subfamily D member 3; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATF: activating transcription factor; ATG: autophagy related; ATM: ATM serine/threonine kinase; BCL2: BCL2 apoptosis regulator; BCL2L11/BIM: BCL2 like 11; BCL2L13: BCL2 like 13; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CANX: calnexin; CAT: catalase; CCPG1: cell cycle progression 1; CHDH: choline dehydrogenase; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke exposure; CTSD: cathepsin D; DDIT3/CHOP: DNA-damage inducible transcript 3; DISC1: DISC1 scaffold protein; DNM1L/DRP1: dynamin 1 like; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 alpha kinase 3; EMD: emerin; EPAS1/HIF-2α: endothelial PAS domain protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBXO27: F-box protein 27; FKBP8: FKBP prolyl isomerase 8; FTD: frontotemporal dementia; FUNDC1: FUN14 domain containing 1; G3BP1: G3BP stress granule assembly factor 1; GBA: glucocerebrosidase beta; HIF1A/HIF1: hypoxia inducible factor 1 subunit alpha; IMM: inner mitochondrial membrane; LCLAT1/ALCAT1: lysocardiolipin acyltransferase 1; LGALS3/Gal3: galectin 3; LIR: LC3-interacting region; LMNA: lamin A/C; LMNB1: lamin B1; LPS: lipopolysaccharide; MAPK8/JNK: mitogen-activated protein kinase 8; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MOD: multiple organelles dysfunction; MTPAP: mitochondrial poly(A) polymerase; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; NLRP3: NLR family pyrin domain containing 3; NUFIP1: nuclear FMR1 interacting protein 1; OMM: outer mitochondrial membrane; OPTN: optineurin; PD: Parkinson disease; PARL: presenilin associated rhomboid like; PEX3: peroxisomal biogenesis factor 3; PGAM5: PGAM family member 5; PHB2: prohibitin 2; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHOT1/MIRO1: ras homolog family member T1; RIPK3/RIP3: receptor interacting serine/threonine kinase 3; ROS: reactive oxygen species; RTN3: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SESN2: sestrin2; SIAH1: siah E3 ubiquitin protein ligase 1; SNCA: synuclein alpha; SNCAIP: synuclein alpha interacting protein; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TICAM1/TRIF: toll-like receptor adaptor molecule 1; TIMM23: translocase of inner mitochondrial membrane 23; TNKS: tankyrase; TOMM: translocase of the outer mitochondrial membrane; TRIM: tripartite motif containing; UCP2: uncoupling protein 2; ULK1: unc-51 like autophagy activating kinase; UPR: unfolded protein response; USP10: ubiquitin specific peptidase 10; VCP/p97: valosin containing protein; VDAC: voltage dependent anion channels; XIAP: X-linked inhibitor of apoptosis; ZNHIT3: zinc finger HIT-type containing 3.

Background: The monitoring and management of blood glucose concentration are standard practices in critical settings as hyperglycaemia has been shown close association with poorer outcomes. Several meta-analyses have revealed that intensive glucose control has no benefit in decreasing short-term mortality among critically ill patients, while the studies these meta-analyses have incorporated have been largely divergent. We aim to perform a more comprehensive meta-analysis addressing this problem to provide stronger evidence. Methods: We conducted comprehensive searches for relevant randomized controlled studies in online databases, including the Cochrane Library, EMBASE, and PubMed databases, up to September 1, 2018. The clinical data, which included all-cause mortality, severe hypoglycemia, need for RRT, infection resulting in sepsis, ICU mortality, 90-day mortality, 180-day mortality, and hospital and ICU lengths of stay, were screened and analyzed after data extraction. We applied odds ratios (ORs) to analyze dichotomous outcomes and mean differences for continuous outcomes with a random effects model. Results: A total of 57 RCTs involving a total of 21840 patients were finally included. Patients admitted to the ICU who underwent intensive glucose control showed significantly reduced all-cause mortality (OR: 0.89; 95% CI: 0.80-1.00; P=0.04; I2=32%), reduced infection rate (OR: 0.65, 95% CI: 0.51-0.82, P=0.0002; I2=47%), a lower occurrence of acquired sepsis (OR: 0.80, 95% CI: 0.65-0.99, P=0.04; I2=0%) and shortened length of ICU stay (MD: -0.70, 95% CI: -1.21--0.19, P=0.007, I2=70%) when compared to the same parameters as those treated with the usual care strategy. However, patients in the intensive glucose control group presented with a significantly higher risk of severe hypoglycemia (OR: 5.63, 95% CI: 4.02-7.87, P

Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.

BackgroundThe incidence of coagulopathy, which was responsible for poor outcomes, was commonly seen among patients with sepsis. In the current study, we aim to determine whether the presence of sepsis-associated coagulopathy (SAC) predicts the clinical outcomes among critically ill patients with postoperative sepsis.MethodsWe conducted a single-center retrospective cohort study by including patients with sepsis admitted to surgical ICU of Chinese PLA General Hospital from January 1, 2014 to December 31, 2018. Baseline characteristics and clinical outcomes were compared with respect to the presence of SAC. Kaplan-Meier analysis was applied to calculate survival rate, and Log-rank test was carried out to compare the differences between two groups. Furthermore, multivariable Cox and logistic and linear regression analysis were performed to assess the relationship between SAC and clinical outcomes, including hospital mortality, development of septic shock, and length of hospital stay (LOS), respectively. Additionally, both sensitivity and subgroup analyses were performed to further testify the robustness of our findings.ResultsA total of 175 patients were included in the current study. Among all included patients, 41.1% (72/175) ICU patients were identified as having SAC. In-hospital mortality rates were significantly higher in the SAC group when compared to that of the No SAC group (37.5% vs. 11.7%; p < 0.001). By performing univariable and multivariable regression analyses, presence of SAC was demonstrated to significantly correlate with an increased in-hospital mortality for patients with sepsis in surgical ICU [Hazard ratio (HR), 3.75; 95% Confidence interval (CI), 1.90–7.40; p < 0.001]. Meanwhile, a complication of SAC was found to be the independent predictor of the development of septic shock [Odds ratio (OR), 4.11; 95% CI, 1.81–9.32; p = 0.001], whereas it was not significantly associated with prolonged hospital LOS (OR, 0.97; 95% CI, 0.83–1.14; p = 0.743).ConclusionThe presence of SAC was significantly associated with increased risk of in-hospital death and septic shock among postoperative patients with sepsis admitted to ICU. Moreover, there was no statistical difference of hospital LOS between the SAC and no SAC groups.

Protein homeostasis is well accepted as the prerequisite for proper operation of various life activities. As the main apparatus of protein translation, ribosomes play an indispensable role in the maintenance of protein homeostasis. Nevertheless, upon stimulation of various internal and external factors, malfunction of ribosomes may be evident with the excessive production of aberrant proteins, accumulation of which can result in deleterious effects on cellular fate and even cell death. Ribosomopathies are characterized as a series of diseases caused by abnormalities of ribosomal compositions and functions. Correspondingly, cell evolves several ribosome quality control mechanisms in maintaining the quantity and quality of intracellular ribosomes, namely ribosome quality control system (RQCS). Of note, RQCS can tightly monitor the entire process from ribosome biogenesis to its degradation, with the capacity of coping with ribosomal dysfunction, including misassembled ribosomes and incorrectly synthesized ribosomal proteins. In the current literature review, we mainly introduce the RQCS and elaborate on the underlying pathogenesis of several ribosomopathies. With the in-depth understanding of ribosomal dysfunction and molecular basis of RQCS, therapeutic strategy by specifically targeting RQCS remains a promising option in treating patients with ribosomopathies and other ribosome-associated human diseases.

Zhufeng Zhang,1 Dongmei Guo,2 Qi Ren3 1Emergency Department of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Radiology Department of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Qi Ren Intensive Care Unit of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qi RenIntensive Care Unit of Sandun District of Zhejiang Hospital, 1229th Gudun Road, Xihu District, Hangzhou, Zhejiang, 310030, People’s Republic of ChinaTel +86-18600754832Email xiewenzhangrenqi@163.comAbstract: Cases of acute tonsillitis, a common disease in the emergency department, are mostly mild and those complicated by severe pneumonia and acute respiratory distress syndrome are rarely reported.Keywords: acute tonsillitis, severe pneumonia, acute respiratory distress syndrome, extracorporeal membrane oxygenation, case report

BackgroundMultiple Organ Dysfunction Syndrome (MODS) is a major cause of high morbidity and mortality among patients in intensive care units (ICU). Although numerous basic and clinical researches on MODS have been conducted, there is still a long way to go to prevent patients from entering this stage. To our knowledge, no bibliometric analyses of MODS have been reported, this study, therefore, was conducted to reveal MODS research status and trends during 2001–2021.MethodsAll relevant literature covering MODS during 2001–2021 were extracted from Web of Science. An online analysis platform of literature metrology was used to analyze the publication trends. VOSviewer software was used to collect and analyze the keywords and research hotspots related to MODS.ResultsAs of July 31, 2021, a total of 994 MODS-related articles from 2001 to 2021 were identified. The United States accounted for the largest number of publications (31.1%), followed by China and Germany, with 186 and 75 publications, respectively. Among all the institutions, the University of Pittsburgh published the most papers related to MODS (21). Critical Care Medicine published the most papers in this field (106). Professor Moore EE, who had the most citation frequency (1847), made great achievements in MODS research. Moreover, analysis of the keywords identified three MODS research hotspot clusters: “mechanism-related research,” “clinical research,” and “diagnostic research.”ConclusionsThe United States maintained a top position worldwide and made the most outstanding contribution in the MODS field. In terms of publication, China was next only to the United States, but there was a disproportion between the quantity of publications and citation frequency. The institution University of Pittsburgh and journal Critical Care Medicine represent the highest level of research in this field. During the 20 years from 2001 to 2021, basic MODS research has been in-depth yet progressed relatively slowly recently, but the outbreak of COVID-19 has to some extent set off an upsurge of clinical research in MODS field.

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

Background: Sepsis can cause unpredictable harm, and early identification of risk for mortality may be conducive to clinical diagnosis. The present study proposes to assess the efficacy of the monocyte/high-density lipoprotein cholesterol ratio (MHR) combined with the neutrophil/lymphocyte ratio (NLR) on the day of admission in predictive efficacy in the 28-day mortality risk in critical patients with sepsis.Material and Methods: We administered observational and retrospective cohort research from a single center. The correlation of the clinical variables, together with the system severity scores of APACHE II and SOFA, are displayed by correlation analysis, and a Cox regression model could be performed to screen the independent risk factors and estimate the capacity of multiple markers in predicting 28-day mortality. The receiver operating characteristic (ROC) curve served as an applied method to output cutoff values for the diagnosis and prognostic risk, and the area under the ROC curve and net reclassification improvement index (NRI), as well as integrated discrimination improvement index (IDI) were employed to assess the feasibility of multiple parameters for predictive value in 28-day mortality of septic patients.Results: The study enrolled 274 eligible patients with sepsis. The correlation analysis indicated NLR and MHR were related to the sepsis severity. A multivariate Cox regression analysis indicated that NLR together with MHR displayed a close relation to death rate after adjusting for other potential confounders (NLR, HR = 1.404 [95% CI 1.170–1.684], P < 0.001; MHR, HR = 1.217 [95% CI 1.112–1.331], P < 0.001). The AUC of NLR, MHR, NLR_MHR was 0.827, 0.876, and 0.934, respectively. The addition on the biomarker NLR_MHR to the prediction model improved IDI by 18.5% and NRI by 37.8%.Conclusions: Our findings suggest that NLR and MHR trend to an elevated level in non-surviving patients with sepsis. Evaluation of NLR_MHR, an independent risk factor for increased mortality, might improve the predictive efficacy for 28-day mortality risk in septic patients.

The question whether the Higgs boson is connected to additional CP violation is one of the driving forces behind precision studies at the Large Hadron Collider. In this work, we investigate the CP structure of the top quark Yukawa interaction-one of the most prominent places for searching for New Physics-through Higgs boson loops in top quark pair production. We calculate the electroweak corrections including arbitrary CP mixtures at next-to-leading-order in the Standard Model Effective Field Theory. This approach of probing Higgs boson degrees of freedom relies on the large $t\bar{t}$ cross section and the excellent perturbative control. In addition, we consider all direct probes with on-shell Higgs boson production in association with a single top quark or top quark pair. This allows us to contrast loop sensitivity versus on-shell sensitivity in these fundamentally different process dynamics. We find that loop sensitivity in $t\bar{t}$ production and on-shell sensitivity in $t\bar{t}H$ and $tH$ provide complementary handles over a wide range of parameter space., updated Fig.2, typos fixed, 10 pages, 8 figures, published version

Black phosphorene and its analogs have attracted intensive attention due to their unique puckered structures, anisotropic characteristics, and negative Poisson's ratio. The van der Waals heterostructures assembly by stacking different materials may show novel physical properties which the parent materials don't possess. In this work, the first-principles calculations were performed to study the mechanical properties of the BP/SnSe van der Waals heterostructure. Interestingly, a near-zero Poisson's ratio vzx was found in BP/SnSe heterostructure. In addition, compared to the parent materials BP and SnSe with strong in-plane anisotropic mechanical properties, the BP/SnSe heterostructure shows strongly suppressed anisotropy. Our findings suggest that the vdW heterostructure could show quite different mechanical properties from the parent materials and provide new opportunities for the mechanical applications of the heterostructures.

Massively bulk RNA sequencing databases incorporating drug screening have opened up an avenue to inform the optimal clinical application of cancer drugs. Meanwhile, the growing single-cell RNA sequencing data contributes to improving therapeutic effectiveness by studying the heterogeneity of drug responses for cancer cell subpopulations. Yet, the drug response information for single-cell data is scarcely obtained. Thus, there is an urgent need to develop computational pipelines to infer and interpret cancer drug response in single cells. Here, we developed scDEAL, a deep transfer learning framework integrating large-scale bulk and single-cell RNA sequencing data. The true innovation of scDEAL is to translate cancer cell line drug response into predicting clinical drug response through the transfer learning between bulk RNA-seq in cancer cells and single cell RNA-seq in clinical samples. The other innovation of scDEAL is the integrated gradient feature interpretation to infer a comprehensive set of signature genes to reveal potential drug resistance mechanisms. We benchmarked scDEAL on six single-cell RNA sequencing datasets and indicate its model interpretability by several case studies. scDEAL not only achieves accurate and robust performance in single-cell drug response predictions, but also can infer signature genes to reveal potential drug resistance mechanisms based on integrated gradient feature interpretation. This work may help study cell reprogramming, drug selection, and repurposing for improving therapeutic efficacy.

Transcription factor EB (TFEB) is a member of the microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) family and critically involved in the maintenance of structural integrity and functional balance of multiple cells. In this review, we described the effects of post-transcriptional modifications, including phosphorylation, acetylation, SUMOylation, and ubiquitination, on the subcellular localization and activation of TFEB. The activated TFEB enters into the nucleus and induces the expressions of targeted genes. We then presented the role of TFEB in the biosynthesis of multiple organelles, completion of lysosome-autophagy pathway, metabolism regulation, immune, and inflammatory responses. This review compiles existing knowledge in the understanding of TFEB regulation and function, covering its essential role in response to cellular stress. We further elaborated the involvement of TFEB dysregulation in the pathophysiological process of various diseases, such as the catabolic hyperactivity in tumors, the accumulation of abnormal aggregates in neurodegenerative diseases, and the aberrant host responses in inflammatory diseases. In this review, multiple drugs have also been introduced, which enable regulating the translocation and activation of TFEB, showing beneficial effects in mitigating various disease models. Therefore, TFEB might serve as a potential therapeutic target for human diseases. The limitation of this review is that the mechanism of TFEB-related human diseases mainly focuses on its association with lysosome and autophagy, which needs deep description of other mechanism in diseases progression after getting more advanced information.

Sepsis has emerged as a global health issue, and accounts for millions of deaths in intensive care units. Dysregulation of the immune response reportedly contributes to the pathogenesis and progression of this lethal condition, which involves both the dysfunction of immune cells and incompetent immunomodulatory mechanisms. High mobility group box 1 (HMGB1) is known as a later inflammatory mediator and is critically involved in the severity and prognosis of sepsis by inducing intractable inflammation and dysfunction of various immune cells. In the present study, we found that intracerebroventricular (ICV) injection of Box A, a specific antagonist of HMGB1, restored the dysregulated response of splenic dendritic cells (DCs) in septic mice by enhancing the expression of surface molecules, including CD80, CD86, and MHC-II, as well as improving DC priming of T lymphocytes. Cerebral HMGB1 was also confirmed to have potent inhibitory effects on DC functions when administrated by ICV injection in normal mice. The brain cholinergic system was found to mediate the immunomodulatory effects of central HMGB1, as it exhibited enhanced activity with persistent HMGB1 exposure. Furthermore, the inhibitory effects of cerebral HMGB1 on the response of peripheral DCs were also blocked by α7nAchR gene knockout. These findings provide novel insight into the relationship between cerebral HMGB1 and splenic DC dysfunction during sepsis, which is, at least in part, dependent on cholinergic system activity.