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Abstract Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.

Heat moisture treatment (HMT) is a widely used method for starch modification due to its safe, green, environmentally friendly, and efficient characteristics. In this study, quinoa starch was modified by HMT with varying moisture contents (20%, 25%, and 30%) at a temperature of 120 °C for 10 hours, and its rheological properties, in vitro digestive properties, and structure were further evaluated. The steady rheology results indicated that all the samples were shear-thinning non-Newtonian fluids. After undergoing HMT, the apparent viscosity of quinoa starch decreased significantly. Additionally, the samples' apparent viscosity decreased as the moisture content of HMT increased. The results of frequency sweep showed that the storage modulus G' of quinoa starch decreased with the increase of moisture content of HMT, while the loss modulus G'', and loss factor increased with the increase of moisture content of HMT. The thixotropic results showed that the thixotropic ring area of quinoa starch decreased with the increase of the moisture content of HMT. Additionally, the results of in vitro digestion showed that the content of rapidly digestible starch in quinoa starch decreased significantly after HMT (P

Abstract Background The Endothelial Activation and Stress Index (EASIX) is a novel marker of endothelial injury and correlates with survival of various patients. The endothelial dysfunction plays an important role on the pathophysiological process of traumatic brain injury (TBI). This study was designed to explore the prognostic value of EASIX on TBI patients. Methods 358 TBI patients hospitalized in the West China hospital between October 2018 and October 2022 were enrolled for this study. The EASIX was calculated based on the formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). The univariate and multivariate logistic regression with forward method was performed to explore the association between EASIX and mortality. A prognostic model was developed combining significant risk factors in the multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the EASIX and the developed model. Results The 30-day mortality of enrolled 358 TBI patients was 51.1%. Non-survivors had higher EASIX than survivors (p

ABSTRACT Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia.IMPORTANCEAs a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

BackgroundThere are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). ObjectiveThis study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. MethodsWe analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. ResultsThe mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P

BackgroundTraumatic brain injury (TBI) is a global health concern that often leads to poor prognosis. We designed this study to explore whether thiamine use is associated with a better prognosis of TBI.MethodsTBI patients selected from the Medical Information Mart for Intensive Care-III database were included in the study. Univariate and multivariate Cox regression analyses were performed to examine the relationship between thiamine use and mortality in TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-thiamine use group and the thiamine use group. Subgroup analysis was performed in the cohort after PSM to verify the association between thiamine use and mortality in TBI patients across different stratifications.ResultsThe incidence of thiamine use in TBI was 18.3%. The thiamine use group had a lower 30-day mortality rate (p < 0.001), a longer length of ICU stay (p < 0.001), and a longer length of hospital stay (p < 0.001) than the non-thiamine use group, both in the primary cohort before PSM and the cohort after PSM. A multivariate Cox regression analysis confirmed that thiamine use was independently associated with mortality (OR = 0.454, p < 0.001) after adjusting for confounding effects. In the cohort after PSM, the subgroup analysis showed that thiamine use is associated with lower mortality in TBI patients with a Glasgow Coma Scale (GCS) score of < 13, but it is not associated with mortality in TBI patients whose GCS score is ≥13.ConclusionThiamine supplementation is effective in improving the outcome of TBI, except in cases of mild TBI. The optimal thiamine supplementation strategy for TBI is worthwhile to be explored in future studies.

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met–GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Objectives: The purpose of this research was to summarize the clinical and prognostic features of cavernous sinus meningiomas (CSM), evaluate the treatment strategies and long-term prognosis of CSM, and improve the management of CSM and the treatment effect for patients. Methods: We retrospectively studied the data of 54 patients who received initial surgical resection and 45 patients who received initial gamma knife radiosurgery (GKRS) for CSM at West China Hospital of Sichuan University from 2009 to 2021. Progression-free survival (PFS), Karnofsky Performance Scale (KPS) scores and neurological function recovery were adopted to assess a comprehensive management strategy for CSM. Results: Gross total resection (GTR) was performed in 51.9 % of cases with 3.7 % surgical mortality. The average follow-up time was 48.7 months, with a progression rate of 29.3 %. The overall improvement rate for cranial nerve function deficits was 50.0 %. By survival analysis, the extent of resection and the histological grade were significantly related to the prognosis. The role of postoperative GKRS is uncertain. For patients who received initial GKRS, the progression rate was 17.8 %, and the overall improvement rate for cranial nerve function deficits was 61.1 %. Primary treatment with GKRS showed better long-term tumor control in patients with CSM (P = 0.046). Conclusions: Maximum safe resection of CSM can improve the neurological function and quality of life of patients, but aggressive resection will cause high perioperative mortality and complication rates. For CSM patients who are suitable for initial gamma knife treatment, choosing GKRS can achieve better long-term tumor control and neurological outcomes.

Objectives: We conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950-2022. Methods: We utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases. Results: Since the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses. Conclusions: Our study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China.

A sensitive and reliable method was developed and validated for the simultaneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS (quick, easy, cheap, effective, rugged and safe) method combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was also applied in the analysis of 23 commonly consumed oilseeds and oil samples. The sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly through 250 mg precipitated silica adsorbent (PSA) and 250 mg C18. The mobile phase was water (containing 0.1% formic acid) and acetonitrile. The external standard protocols were adopted to validate the method in terms of recovery, linearity, precision, sensitivity, and relative standard deviation (RSD) under the optimized conditions. The linear calibration curves with different ranges were established with R2 > 0.997 3, limit of detections (LODs) ranged from 0.100 µg/kg to 2.000 µg/kg and limit of quantitations (LOQs) ranged from 0.300 µg/kg to 6.000 µg/kg. The limit of detection meets the detection requirement for the maximum residue limits in practical samples. Meanwhile, the recoveries ranged from 60.2% to 116.6% with associated RSDs ranged from 0.33% to 5.35% in 10 oilseeds matrices and ranged from 61.9% to 116.9% with RSDs ranged from 0.30% to 5.02% in 13 oil matrices. These features do make the UPLC-MS/MS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

Abstract The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

To study the molecular mechanism of baicalein interrupting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway, molecular docking, molecular dynamics simulation, binding free energy calculation and principal component analysis were first performed to predict the inhibition effect of baicalein on this pathway, which was verified by enzyme-linked immunosorbent assay (ELISA) subsequently. Binding free energy calculations showed that the affinity of baicalein to the PD-L1 dimer was −32.41±0.31 kcal/mol. Free energy decomposition, contact numbers and nonbonded interaction results revealed that baicalein mainly interacted with the C-, C'-, F- and G-sheet domains of the PD-L1 dimer. Importantly, nonpolar interactions between the key residues Tyr56, Met115, Ala121, Asp122 and baicalein were dominant factors during the binding process. Cross-correlation matrixes and secondary structure results further demonstrated that baicalein could stably interact with the sheet domains of the PD-L1 dimer. The result of ELISA showed that the IC50 value of baicalein for inhibiting the PD-1/PD-L1 interaction was 79.47 µg/L. In conclusion, this study revealed that baicalein could directly bind to the PD-L1 dimer, thus blocking the PD-1/PD-L1 interaction, would provide basis for discovering natural small-molecule inhibitors of this pathway.

ABSTRACTStreptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients.MethodsSignificant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC).ResultsAmong 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt–Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt–Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality.ConclusionThe ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Pituitary adenomas and intracranial aneurysms are prevalent neurosurgical conditions, but their simultaneous presence is uncommon, affecting only 0.5%-7.4% of those with pituitary adenomas. The strategy of treating aneurysms endovascularly before removing pituitary adenomas is widely adopted, yet reports on addressing both conditions at once through an endoscopic endonasal approach (EEA) are scarce. We present a case involving a pituitary adenoma coupled with an anterior communicating artery aneurysm. Utilizing the EEA, we excised the adenoma and clipped the aneurysm concurrently. The patient recovered well post-surgery, with follow-up assessments confirming the successful resolution of both the adenoma and aneurysm. We proved the feasibility of the EEA in the treatment of pituitary adenomas with anterior communicating artery aneurysms under specific anatomical relationships and close intraoperative monitoring.

BackgroundBiomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role.MethodsThis prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC).ResultsOf 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p

Background:Traumatic brain injury (TBI) patients suffer high risks of mortality. Ondansetron has been verified to be effective in improving the prognosis of some kinds of critically ill patients. We design this study to explore whether ondansetron use is associated with lower risks of mortality among TBI patients.Methods:TBI patients from the Medical Information Mart for Intensive Care-III were collected. The usage of ondansetron, including intravenous injection and oral tablet, since admission to the Beth Israel Deaconess Medical Center between 2001 and 2012 was identified. Univariate and multivariate logistic regression were performed to analyze the relationship between the ondansetron use and mortality of TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-ondansetron use group and ondansetron use group. Sub-group analysis was performed to verify the association between the ondansetron use and mortality of TBI patients in different TBI severity levels after PSM.Results:In TBI cohorts before PSM, the usage incidence of ondansetron was 37.2%. The 30-day mortality was significantly lower in the ondansetron group (p < 0.001). The multivariate logistic regression showed that ondansetron was associated with the lower mortality of TBI patients (p = 0.008). In TBI cohorts after PSM, the 30-day mortality of the ondansetron group was lower than that of the non-ondansetron group, although without statistical significance (p = 0.079). Logistic regression indicated ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.051). In addition, Cox regression also presented that ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.052).Conclusion:Ondansetron usage is associated with a lower mortality risk of moderate-to-severe TBI but not mild TBI patients. Ondansetron may be a novel adjunctive therapeutic strategy to improve the prognosis of moderate-to-severe TBI patients.

Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.

Based on imbibition replacement of shut-in well in tight oil reservoirs, this paper expounds the principle of saturation rebalancing during the shut-in process after fracturing, establishes an optimization method for shut-in time after horizontal well volume fracturing with the goal of shortening oil breakthrough time and achieving rapid oil breakthrough, and analyzes the influences of permeability, porosity, fracture half-length and fracturing fluid volume on the shut-in time. The oil and water imbibition displacement in the matrix and fractures occurs during the shut-in process of wells after fracturing. If the shut-in time is too short, the oil-water displacement is not sufficient, and the oil breakthrough time is long after the well is put into production. If the shut-in time is too long, the oil and water displacement is sufficient, but the energy dissipation in the formation near the bottom of the well is severe, and the flowing period is short and the production is low after the well is put into production. A rational shut-in time can help shorten the oil breakthrough time, extend the flowing period and increase the production of the well. The rational shut-in time is influenced by factors such as permeability, porosity, fracture half-length and fracturing fluid volume. The shortest and longest shut-in times are negatively correlated with porosity, permeability, and fracture half-length, and positively correlated with fracturing fluid volume. The pilot test in tight oil horizontal wells in the Songliao Basin, NE China, has confirmed that the proposed optimization method can effectively improve the development effect of horizontal well volume fracturing.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus to cause acute respiratory distress syndrome (ARDS) and contains four structural proteins: spike, envelope, membrane, and nucleocapsid. An increasing number of studies have demonstrated that all four structural proteins of SARS-CoV-2 are capable of causing lung injury, even without the presence of intact virus. Therefore, the topic of SARS-CoV-2 structural protein-evoked lung injury warrants more attention. In the current article, we first synopsize the structural features of SARS-CoV-2 structural proteins. Second, we discuss the mechanisms for structural protein-induced inflammatory responses in vitro. Finally, we list the findings that indicate structural proteins themselves are toxic and sufficient to induce lung injury in vivo. Recognizing mechanisms of lung injury triggered by SARS-CoV-2 structural proteins may facilitate the development of targeted modalities in treating COVID-19.

BackgroundGlioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment.MethodsTCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan–Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection.ResultsBoth transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages.ConclusionIL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.

Abstract Aims This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment. Main methods Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues. Key findings We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells. Significance This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment.

Since its emergence, SARS-CoV-2 virus, the causative agent of COVID-19, has undergone over three years of evolutionary changes. Throughout this evolutionary process, multiple variants, such as Alpha, Beta, Gamma, Delta, and Omicron, have emerged, leading to widespread outbreaks and pandemics. A comprehensive analysis of the evolution of SARS-CoV-2 over the past three years reveals its progression through three distinct stages.

Abstract High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions.

Rapid detection of target foodborne pathogens plays more and more significant roles in food safety, which requires the efficiency, sensitivity, and accuracy. In this research, we proposed a new strategy of isothermal-molecular-amplification integrated with lateral-flow-strip for rapid detection of Salmonella without traditional enrichment-culture. The designed syringe-assisted-filtration can contribute to simultaneous collection and concentration of target bacterium from vegetable samples in just 3 min, resolving the drawbacks of traditional random sampling protocols. After simple and convenient ultrasonication, samples can be directly amplified at 39 °C in 25 min and the amplicons are qualitatively and quantitatively analyzed with the designed lateral-flow-strip in 5 min. Finally, satisfied results have been achieved within 40 min, which greatly improve the efficiency while the accuracy is also guaranteed. Furthermore, all detection steps can be completed under instrument-free conditions. This method will hold great promise for target pathogen detection in the resource-limited district, or for emergency on-site identification.

Raman spectroscopy for rapid identification of foodborne pathogens based on phenotype has attracted increasing attention, and the reliability of the Raman fingerprint database through genotypic determination is crucial. In the research, the classification model of four foodborne pathogens was established based on t-distributed stochastic neighbor embedding (t-SNE) and support vector machine (SVM); the recognition accuracy was 97.04%. The target bacteria named by the model were ejected through Raman-activated cell ejection (RACE), and then single-cell genomic DNA was amplified for species analysis. The accuracy of correct matches between the predicted phenotype and the actual genotype of the target cells was at least 83.3%. Furthermore, all anticipant sequencing results brought into correspondence with the species were predicted through the model. In sum, the Raman fingerprint database based on Raman spectroscopy combined with machine learning was reliable and promising in the field of rapid detection of foodborne pathogens.

Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of Pediococcus pentosaceus MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1β, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as Ruminococcus, while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that Pediococcus pentosaceus MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.

Abstract Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe‐set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.

In order to explore the emulsifying effect of micronization technology on carrot residue and fully develop the utilization value of carrot pomace. In this study, carrot residue was used as the experimental material to obtain different level carrot residue powder with different grinding time. Compared with the effect of carrot residue added and oil-water ratio on the stability and emulsification of the carrot residue powder emulsion, the best carrot dietary fiber emulsion conditions were obtained, and the emulsion was prepared under this condition. The effects of pH, NaCl concentration and temperature on the emulsification, stability and emulsion index of the emulsion were studied. The experimental results showed that grinding had changed the morphological structure of carrot residue, and the particle size had not been further reduced after the grinding time was 30 min. The emulsification ability and stability of carrot residue showed a tendency to rise first and then decreased with the extension of grinding time. When the grinding time was 30 minutes, the emulsification and stability of the emulsion were the best. At the same time, under the best emulsifier, the best oil-water ratio (2:8) and carrot residue concentration (3%), the EAI and ESI reach 60.05 m2/g and 60.64 min, and the emulsification increased with the pH value, stability increased with the pH value firstly, slightly reduced at pH6 and then enhanced. They decreased with the increase of NaCl concentration. And the emulsification increased and then decreased with the increase of temperature, stability decreased. Micronized carrot residue has good ability to stabilize emulsion and has the potential to be used as a food-grade emulsion stabilizer.

Objectives: From March to June 2021, the reported number of clinically diagnosed endemic typhus in Anhui and Hubei provinces of China nearly increased four-fold compared with the monthly average numbers in last 5 years. An etiological and epidemiological investigation was initiated. Methods: The clinical specimens from the reported patients and the potential vector ticks were collected for molecular and serological detection, as well as cell culturing assay to identify the potential pathogen. Results: Polymerase chain reaction and sequence analysis of rrs and groEL showed that the pathogen from these patients was Ehrlichia sp., isolated from Haemaphysalis longicornis attached to these patients. The phylogenetic analysis based on 39 Ehrlichia genomes suggested that it should be taxonomically classified as a novel species, tentatively named “Candidatus Ehrlichia erythraense”. A total of 19 of 106 cases were confirmed as Candidatus Ehrlichia erythraense infections by polymerase chain reaction, sequencing, and/or serological tests. The most frequent symptoms were fever (100%), rashes (100%), asthenia (100%), anorexia (100%), and myalgia (79%). Conclusion: The occurrence of the disease presenting with fever and rashes in Anhui and Hubei provinces was caused by a novel species of the genus Ehrlichia; physicians need to be aware of this newly-discovered pathogen to ensure appropriate testing, treatment, and regional surveillance.

Abstract Background Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. Methods In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. Results Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. Conclusions Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

BackgroundConvolutional neural networks (CNNs) have produced state-of-the-art results in meningioma segmentation on magnetic resonance imaging (MRI). However, images obtained from different institutions, protocols, or scanners may show significant domain shift, leading to performance degradation and challenging model deployment in real clinical scenarios. ObjectiveThis research aims to investigate the realistic performance of a well-trained meningioma segmentation model when deployed across different health care centers and verify the methods to enhance its generalization. MethodsThis study was performed in four centers. A total of 606 patients with 606 MRIs were enrolled between January 2015 and December 2021. Manual segmentations, determined through consensus readings by neuroradiologists, were used as the ground truth mask. The model was previously trained using a standard supervised CNN called Deeplab V3+ and was deployed and tested separately in four health care centers. To determine the appropriate approach to mitigating the observed performance degradation, two methods were used: unsupervised domain adaptation and supervised retraining. ResultsThe trained model showed a state-of-the-art performance in tumor segmentation in two health care institutions, with a Dice ratio of 0.887 (SD 0.108, 95% CI 0.903-0.925) in center A and a Dice ratio of 0.874 (SD 0.800, 95% CI 0.854-0.894) in center B. Whereas in the other health care institutions, the performance declined, with Dice ratios of 0.631 (SD 0.157, 95% CI 0.556-0.707) in center C and 0.649 (SD 0.187, 95% CI 0.566-0.732) in center D, as they obtained the MRI using different scanning protocols. The unsupervised domain adaptation showed a significant improvement in performance scores, with Dice ratios of 0.842 (SD 0.073, 95% CI 0.820-0.864) in center C and 0.855 (SD 0.097, 95% CI 0.826-0.886) in center D. Nonetheless, it did not overperform the supervised retraining, which achieved Dice ratios of 0.899 (SD 0.026, 95% CI 0.889-0.906) in center C and 0.886 (SD 0.046, 95% CI 0.870-0.903) in center D. ConclusionsDeploying the trained CNN model in different health care institutions may show significant performance degradation due to the domain shift of MRIs. Under this circumstance, the use of unsupervised domain adaptation or supervised retraining should be considered, taking into account the balance between clinical requirements, model performance, and the size of the available data.

Meat adulteration-based food fraud has recently become one of the global major economical, illegal, religious, and public health concerns. In this work, we developed a microarray chip polymerase chain reaction (PCR)-directed microfluidic lateral flow strip (LFS) device that facilitates the accurate and simultaneous identification of beef adulterated with chicken, duck, and pork, especially in processed beef products. To realize this goal, four pairs of amplification primers were designed and applied for specifically amplifying genomic DNA extracted from mixed meat powders in microarray chip. With the prominent advantage of this device lies in the flexible combination and integration of sample loading, detection, and reporting in microstructures, all the DNA amplicons can be individually visualized on the LFS unit, leading to the appearance of test lines (TC line, TD line, TP line, or TB line) as well as the control line (C line) for the species identification and quantification in beef products. Based on this new method, the adulterants were successfully distinguished and identified in mixtures down to 0.01% (wt.%) while the carryover aerogel contamination in routine molecular diagnostic laboratories was effectively avoided. The practicability, accuracy, and reliability of the device were further confirmed by using real-time PCR as a gold standard control on the successful identification of 50 processed ground meat samples sourced from local markets. The method and device proposed herein could be a useful tool for on-site identification of food authentication.

ABSTRACTEmerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαβR-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77–88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).

The prediction system EpiSIX was used to study the COVID-19 epidemic in mainland China between November 2022 and January 2023, based on reported data from December 9, 2022, to January 30, 2023, released by The Chinese Center for Disease Control and Prevention on February 1, 2023. Three kinds of reported data were used for model fitting: the daily numbers of positive nucleic acid tests and deaths, and the daily number of hospital beds taken by COVID-19 patients. It was estimated that the overall infection rate was 87.54% and the overall case fatality rate was 0.078%–0.116% (median 0.100%). Assuming that a new COVID-19 epidemic outbreak would start in March or April of 2023, induced by a slightly more infectious mutant strain, we predicted a possible large rebound between September and October 2023, with a peak demand of between 800,000 and 900,000 inpatient beds. If no such new outbreak was induced by other variants, then the current COVID-19 epidemic course in mainland China would remain under control until the end of 2023. However, it is suggested that the necessary medical resources be prepared to manage possible COVID-19 epidemic emergencies in the near future, especially for the period between September and October 2023.

On December 7, 2022, China adjusted public health control measures, there have been widespread of SARS-CoV-2 infections in Chinese mainland. As the number of infected people increased, the mutation probability of SARS-CoV-2 is also raised. Therefore, it is of great importance to monitor SARS-CoV-2 variants and its mutations in China. In this current study, 665 SARS-CoV-2 genomes from China deposited in the public database were used to analyze the proportion of different variants; to determine the composition of variants in China across different provinces; and analyze specific mutation frequency, focusing on 12 immune escape residues. The results showed that no new mutations were generated on the 12 immune escape residues. The evolutionary analysis of the BF.7 variant circulating in China showed that there is an independent evolutionary branch with unique mutation sites, officially named BF.7.14 by PANGO. This variant may have been imported from Russia to Inner Mongolia at the end of September 2022 and continued its spread in China. The evolutionary analysis of BA.5.2 variant shows that the variant is composed of two sub-variants, named BA.5.2.48 and BA.5.2.49 by PANGO, respectively. This variant may have been imported from abroad to Beijing at the beginning of September 2022 and formed two sub-variants after domestic transmission. Finally, this study showed that current epidemic variants in China were already circulating in other countries, and there were no additional mutations on immune escape residues that could pose a threat to other countries.

The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.

As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular localization patterns of this complex are largely unknown. Since different subsets of mRNAs are translated in distinct subcellular compartments, understanding the distribution of translation initiation factors in the cell is of major interest. Here, we developed an in situ detection method for eIF4F at the single cell level. By using an image-based spot feature analysis pipeline as well as supervised machine learning, we identify five distinct spatial patterns of the eIF4F translation initiation complex in human melanoma cells. The quantity of eIF4F complex per cell correlated with the global mRNA translation activity, and its variation is dynamically regulated by cell state or extracellular stimuli. In contrast, the spatial patterns of eIF4F complexes at the single cell level could distinguish melanoma cells harboring different oncogenic driver mutations. This suggests that different tumorigenic contexts differentially regulate the subcellular localization of mRNA translation, with specific localization of eIF4F potentially associated with melanoma cell chemoresistance.

We report a case-series study of 5 patients with Japanese spotted fever from the Three Gorges Area in China, including 1 fatal case. Seroprevalence of Rickettsia japonica was ≈21% among the local population. Our report highlights the emerging potential threat to human health of Japanese spotted fever in the area.

Jujube residue is an abundant and low-cost dietary fiber resource, but its relatively lower hydration and functional properties limit its utilization as an ingredient of functional food. Thus, cellulase and hemicellulase hydrolysis, enzymatic hydrolysis assisted by phosphate grafting (EPG), and enzymatic hydrolysis assisted by acrylate grafting (EAG) were used to improve the functional properties of jujube residue dietary fiber (JRDF) in this study. The results evidenced that these modifications all increased the porosity of the microstructure of JRDF and increased the soluble fiber content, surface area, and hydration properties, but reduced its brightness (p < 0.05). Moreover, JRDF modified by enzymolysis combined with acrylate grafting offered the highest extractable polyphenol content, oil, sodium cholate, and nitrite ion sorption abilities. Meanwhile, JRDF modified via enzymolysis assisted by phosphate grafting showed the highest soluble fiber content (23.53 g∙100 g−1), water-retention ability (12.84 g∙g−1), viscosity (9.37 cP), water-swelling volume (10.80 mL∙g−1), and sorption ability of copper (II) and lead (II) ions. Alternatively, JRDF modified with cellulase hydrolysis alone exhibited the highest glucose adsorption capacity (21.9 g∙100 g−1) at pH 7.0. These results indicate that EPG is an effective way to improve the hypolipidemic effects of JRDF, while EAG is a good choice to enhance its hydration and hypoglycemic properties.

PurposeAccurate prediction of urinary tract infection (UTI) following intracerebral hemorrhage (ICH) can significantly facilitate both timely medical interventions and therapeutic decisions in neurocritical care. Our study aimed to propose a machine learning method to predict an upcoming UTI by using multi-time-point statistics.MethodsA total of 110 patients were identified from a neuro-intensive care unit in this research. Laboratory test results at two time points were chosen: Lab 1 collected at the time of admission and Lab 2 collected at the time of 48 h after admission. Univariate analysis was performed to investigate if there were statistical differences between the UTI group and the non-UTI group. Machine learning models were built with various combinations of selected features and evaluated with accuracy (ACC), sensitivity, specificity, and area under the curve (AUC) values.ResultsCorticosteroid usage (p < 0.001) and daily urinary volume (p < 0.001) were statistically significant risk factors for UTI. Moreover, there were statistical differences in laboratory test results between the UTI group and the non-UTI group at the two time points, as suggested by the univariate analysis. Among the machine learning models, the one incorporating clinical information and the rate of change in laboratory parameters outperformed the others. This model achieved ACC = 0.773, sensitivity = 0.785, specificity = 0.762, and AUC = 0.868 during training and 0.682, 0.685, 0.673, and 0.751 in the model test, respectively.ConclusionThe combination of clinical information and multi-time-point laboratory data can effectively predict upcoming UTIs after ICH in neurocritical care.

The COVID-19 epidemic in December 2019 had a significant negative impact on people’s health and economies all across the world. The most effective preventive measure against COVID-19 is vaccination. Therefore, the development and production of COVID-19 vaccines is booming worldwide. This study aimed to analyze the current state of that research and its development tendency by bibliometrics. We conducted a thorough search of the Web of Science Core Collection. VOSviewer1.6.18 was used to perform the bibliometric analysis of these papers. A total of 6,325 papers were finally included. The USA maintained a top position worldwide. Shimabukuro Tom T and Harvard University were the most prolific author and institution. The Vaccines was the most published journal. The research hotspots of COVID-19 vaccines can be classified into vaccine hesitancy, vaccine safety and effectiveness, vaccine immunogenicity, and adverse reactions to vaccines. Studies on various vaccination types have also concentrated on efficacy against continuously developing virus strains, immunogenicity, side effects, and safety.

The World Health Organization (WHO) declared monkeypox as a public health emergency of international concern (PHEIC) on July 23, 2022, their highest level of alert. This raised concerns about the management of the global monkeypox outbreak, as well as the scientific analysis and accurate prediction of the future course of the epidemic. This study used EpiSIX (an analysis and prediction system for epidemics based on a general SEIR model) to analyze the monkeypox epidemic and to forecast the major tendencies based on data from the USA CDC (https://www.cdc.gov) and the WHO (https://www.who.int/health-topics/monkeypox). The global outbreak of monkeypox started in the UK on May 2, 2022, which marked the beginning of an epidemic wave. As of October 28, 2022, the cumulative number of reported cases worldwide was 77,115, with 36 deaths. EpiSIX simulations predict that the global monkeypox epidemic will enter a low epidemic status on March 1, 2023 with the cumulative number of confirmed cases ranging from 85,000 to 124,000, and the total number of deaths ranging from 60 to 87. Our analysis revealed that the basic reproduction number (R0) of monkeypox virus (MPXV) is near to 3.1 and the percentage of asymptomatic individuals is 13.1 %–14.5 %, both of which are similar to the data for SARS. The vaccination efficiency against susceptibility (VEs) of individuals who have had monkeypox is ∼ 79 %, and the vaccination efficiency against infectiousness (VEi) of individuals who have had monkeypox is ∼ 76 %–82 %. The mean incubation period for monkeypox is 8 days. In total, 94.7 % of infected individuals develop symptoms within 20 days and recover within 2 weeks after the confirmation of symptoms. Simulation results using EpiSIX showed that ring vaccination was remarkably effective against monkeypox. Our findings confirmed that a 20-day isolation for close contacts is necessary.

The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The “what-if” scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.

Over the past two years, scientists throughout the world have completed more than 6 million SARS-CoV-2 genome sequences. Today, the number of SARS-CoV-2 genomes exceeds the total number of all other viral genomes. These genomes are a record of the evolution of SARS-CoV-2 in the human host, and provide information on the emergence of mutations. In this study, analysis of these sequenced genomes identified 296,728 de novo mutations (DNMs), and found that six types of base substitutions reached saturation in the sequenced genome population. Based on this analysis, a “mutation blacklist” of SARS-CoV-2 was compiled. The loci on the “mutation blacklist” are highly conserved, and these mutations likely have detrimental effects on virus survival, replication, and transmission. This information is valuable for SARS-CoV-2 research on gene function, vaccine design, and drug development. Through association analysis of DNMs and viral transmission rates, we identified 185 DNMs that positively correlated with the SARS-CoV-2 transmission rate, and these DNMs where classified as the “mutation whitelist” of SARS-CoV-2. The mutations on the “mutation whitelist” are beneficial for SARS-CoV-2 transmission and could therefore be used to evaluate the transmissibility of new variants. The occurrence of mutations and the evolution of viruses are dynamic processes. To more effectively monitor the mutations and variants of SARS-CoV-2, we built a SARS-CoV-2 mutation and variant monitoring and pre-warning system (MVMPS), which can monitor the occurrence and development of mutations and variants of SARS-CoV-2, as well as provide pre-warning for the prevention and control of SARS-CoV-2 (https://www.omicx.cn/). Additionally, this system could be used in real-time to update the “mutation whitelist” and “mutation blacklist” of SARS-CoV-2.

Between November 2021 and January 2022, four patients of community-acquired pneumonia were admitted to the hospitals in Lishui city, Zhejiang province, China. Their main clinical manifestations were fever and dry cough as well as radiographic infiltrate, but the empiric antimicrobial therapy or traditional Chinese medicine was not effective for their illness. Clinical specimens from the patients as well as environmental and poultry specimens were collected for the determination of the causative pathogen. The ompA gene and seven housekeeping genes of Chlamydia psittaci were successfully amplified from all the patients, and the sequences of each gene were identical to one another, suggesting that they were infected by the same strain of C. psittaci. A novel strain of C. psittaci (LS strain) was isolated from the bronchoalveolar lavage fluid of patient 2 and its whole genome was obtained. Phylogenetic analyses based on the whole-genome sequences showed that the isolate is most closely related to the strain (WS/RT/E30) identified as genotype E/B. In addition, The ompA gene and four housekeeping genes of C. psittaci were also amplified from two of four faeces samples of geese at the home of patient 2, and the sequences from geese were 100% identical to those from the patients. Accordingly, these cases could be attributed to a circulating C. psittaci strain of genotype E/B in the local geese. Therefore, there is an urgent need to strengthen the regional surveillance on C. psittaci among poultry and humans for prevention and control of the outbreak of psittacosis in the city.

The enteroinvasive bacterium Shigella flexneri is known as a highly host-adapted human pathogen. There had been no known other reservoirs reported until recently. Here 34 isolates obtained from animals (yaks, dairy cows and beef cattle) from 2016 to 2017 and 268 human S. flexneri isolates from China were sequenced to determine the relationships between animal and human isolates and infer the evolutionary history of animal-associated S. flexneri. The 18 animal isolates (15 yak and 3 beef cattle isolates) in PG1 were separated into 4 lineages, and the 16 animal isolates (1 yak, 5 beef cattle and 10 dairy cow isolates) in PG3 were clustered in 8 lineages. The most recent human isolates from China belonged to PG3 whereas Chinese isolates from the 1950s–1960s belonged to PG1. PG1 S. flexneri may has been transmitted to the yaks during PG1 circulation in the human population in China and has remained in the yak population since, while PG3 S. flexneri in animals were likely recent transmissions from the human population. Increased stability of the large virulence plasmid and acquisition of abundant antimicrobial resistance determinants may have enabled PG3 to expand globally and replaced PG1 in China. Our study confirms that animals may act as a reservoir for S. flexneri. Genomic analysis revealed the evolutionary history of multiple S. flexneri lineages in animals and humans in China. However, further studies are required to determine the public health threat of S. flexneri from animals.