Electronic Modulation of Doped MoS2 Nanosheets for Improved CO2 Sensing and Capture.

Transition-metal dichalcogenides (TMDs) are widely used in the gas sensing field, owing to their high surface-to-volume ratio enabled by the two-dimensional (2D) structure, adjustable band gap, and high electron transfer. However, it is challenging for TMD materials to realize superior CO2 sensing, due to their weak CO2 adsorption capacity. Herein, we predict through density functional theory (DFT) calculations that rare earth metal doping is an effective strategy to boost the CO2 sensing capability of TMDs. As a proof-of-concept, we investigate and find that the introduction of rare earth metal atoms (La, Ce, Pr, or Nd) can induce lattice strain and modulate the electronic properties of MoS2. When negative charges are injected in rare earth metal doped MoS2 (R-MoS2), the 5d or 4f orbital of the rare earth metal atom in R-MoS2 can produce a stronger orbital hybridization with 2p orbitals of C and O in CO2. Therefore, the CO2 adsorption is significantly enhanced and the charge transfer is facilitated for negatively charged R-MoS2. Moreover, negatively charged R-MoS2 exhibits an excellent CO2 selectivity. Our results indicate that the rare earth metal doping and electronic modulation in 2D materials may provide a new pathway for CO2 sensing and capture.

HER2-CD3-Fc Bispecific Antibody-Encoding mRNA Delivered by Lipid Nanoparticles Suppresses HER2-Positive Tumor Growth.

The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common. More potent and durable HER2-targeted therapies are desperately needed for patients with HER2-positive cancers. In this study, we developed a lipid nanoparticle (LNP)-based therapy formulated with mRNA encoding a novel HER2-CD3-Fc bispecific antibody (bsAb) for HER2-positive cancers. The LNPs efficiently transfected various types of cells, such as HEK293S, SKOV-3, and A1847, leading to robust and sustained secretion of the HER2-CD3-Fc bsAb with high binding affinity to both HER2 and CD3. The bsAb induced potent T-cell-directed cytotoxicity, along with secretion of IFN-λ, TNF-α, and granzyme B, against various types of HER2-positive tumor cells in vitro, including A549, NCI-H460, SKOV-3, A1847, SKBR3, and MDA-MB-231. The bsAb-mediated antitumor effect is highly specific and strictly dependent on its binding to HER2, as evidenced by the gained resistance of A549 and A1847 her2 knockout cells and the acquired sensitivity of mouse 4T1 cells overexpressing the human HER2 extracellular domain (ECD) or epitope-containing subdomain IV to the bsAb-induced T cell cytotoxicity. The bsAb also relies on its binding to CD3 for T-cell recruitment, as ablation of CD3 binding abolished the bsAb's ability to elicit antitumor activity. Importantly, intratumoral injection of the HER2-CD3-Fc mRNA-LNPs triggers a strong antitumor response and completely blocks HER2-positive tumor growth in a mouse xenograft model of human ovarian cancer. These results indicate that the novel HER2-CD3-Fc mRNA-LNP-based therapy has the potential to effectively treat HER2-positive cancer.

Impact of Heat Treatment on the Mechanical Properties and Fracture Morphology of Ti555211 Alloy.

Heat treatment is important for optimizing the strength performance and improving the toughness of titanium alloys. In this study, we investigated the impact of three heat treatment methods (ß-annealing, double annealing, and solid-solution and aging treatment) on the mechanical properties and fracture morphology of Ti555211 titanium alloy. The results show that after ß-annealing treatment, the alloy retains a high strength, while showing almost no ductility, and no yield strength. The alloy after double annealing has a high elongation rate (~54%) and lower strength. After solid-solution and aging heat treatment, the alloy was able to retain both high strength and a certain degree of ductility. The optimal heat-treatment process is solid-solution treatment at 820 °C/2 h and aging at 560 °C/12 h, which results in a maximum tensile strength of 1404 MPa and an elongation rate of 11%.

Cerebral venous sinus thrombosis accompanied by cerebral venous infarction and multiorgan dysfunction after wasp stings, A case report.

Introduction: The high incidence of wasp stings have been causing a variety of injuries in China, but systemic complications are rarely reported. Case presentation: A 59-year-old man was severely attacked by wasps. He developed an acute onset of right hemiplegia and chest distress and was admitted to our emergency department 13 hours after being attacked. Various abnormal signals were found by biochemical tests. Magnetic resonance venography of head demonstrated that the superior sagittal sinus was not visible, indicating cerebral venous sinus thrombosis. Magnetic resonance imaging showed abnormal signals in the left frontal lobe, parietal lobe, and thalamus, indicating venous cerebral infarction and hemorrhage, coupled with subarachnoid hemorrhage. The patient was diagnosed with a rare combination of cerebral venous sinus thrombosis, cerebral venous infarction, and multi-organ dysfunction following hornet stings. After undergoing systematic treatment including blood perfusion, blood dialysis, anti-inflammatory hormone therapy, antiallergic medication, antibiotic use, and anticoagulation treatment, the patient showed significant improvement in limb muscle strength and dizziness symptoms. However, the patient developed irreversible kidney damage and is currently dependent on renal replacement therapy. Conclusions: This case highlights the serious systemic consequences that can occur following multiple wasp stings, including rare complications such as venous sinus thrombosis leading to cerebral infarction and renal failure. Early intervention with blood perfusion, hemodialysis, and plasmapheresis, in addition to general treatment, may help prevent permanent organ damage in patients with a large number of wasp stings.

Optimization of polyethylene terephthalate biodegradation using a self-assembled multi-enzyme cascade strategy.

Although many efforts have been devoted to the modification of polyethylene terephthalate (PET) hydrolases for improving the efficiency of PET degradation, the catalytic performance of these enzymes at near-ambient temperatures remains a challenge. Herein, a multi-enzyme cascade system (PT-EC) was developed and validated by assembling three well-developed PETases, PETaseEHA, Fast-PETase, and Z1-PETase, respectively, together with carboxylesterase TfCa, and hydrophobic binding module CBM3a using scaffold proteins. The resulting PT-ECEHA, PT-ECFPE, PT-ECZPE all demonstrated outstanding PET degradation efficacy. Notably, PT-ECEHA exhibited a 16.5-fold increase in product release compared to PETaseEHA, and PT-ECZPE yielded the highest amount of product. Subsequently, PT-ECs were displayed on the surface of Escherichia coli, respectively, and their degradation efficiency toward three PET types was investigated. The displayed PT-ECEHA exhibited a 20-fold increase in degradation efficiency with PET film compared to the surface-displayed PETaseEHA. Remarkably, an almost linear increase in product release was observed for the displayed PT-ECZPE over a one-week degradation period, reaching 11.56 ± 0.64 mM after 7 days. TfCaI69W/L281Y evolved using a docking-based virtual screening strategy showed a further 2.5-fold increase in the product release of PET degradation. Collectively, these advantages of PT-EC demonstrated the potential of a multi-enzyme cascade system for PET bio-cycling.

White Matter Hyperintensity is Associated with Malignant Cerebral Edema in Ischemic Stroke Treated with Thrombectomy.

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

ZnIn2S4 Nanosheets for Efficient NO2 Detection at Room Temperature: Insights into the Role of Sulfur Vacancies.

Engineering atomic vacancies in metal sulfide semiconductors allows for the efficient tuning of their electronic and chemical properties. In this work, we synthesized hollow tubular structures constructed by bimetallic ZnIn2S4 using a metal-organic framework (MOF) as the template. We found that the sulfur vacancies in ZnIn2S4 enabled extremely fast NO2 detection with high response at room temperature (RT), and the material with high sulfur vacancy content delivers a 2 times higher response to 10 ppm NO2 than the device with low sulfur vacancy content. To unveil the crucial role played by sulfur vacancies, DFT calculations were conducted to reveal that sulfur vacancies greatly enhance the interaction and electron transfer between ZnIn2S4 and NO2. This study will provide hints for the engineering of bimetallic sulfide materials for low-power gas sensors at RT.

Stabilizing Single-Atom Pt on Fe2O3 Nanosheets by Constructing Oxygen Vacancies for Ultrafast H2 Sensing.

Single-atom catalysts (SACs) hold great promise in highly sensitive and selective gas sensors due to their ultrahigh atomic efficiency and excellent catalytic activity. However, due to the extremely high surface energy of SACs, it is still a huge challenge to synthesize a stable single-atom metal on sensitive materials. Here, we report an atomic layer deposition (ALD) strategy for the elaborate synthesis of single-atom Pt on oxygen vacancy-rich Fe2O3 nanosheets (Pt-Fe2O3-Vo), which displayed ultrafast and sensitive detection to H2, achieving the stability of Pt single atoms. Gas-sensing investigation showed that the Pt-Fe2O3-Vo materials enabled a significantly enhanced response of 26.5-50 ppm of H2, which was 17-fold higher than that of pure Fe2O3, as well as ultrafast response time (2 s), extremely low detection limit (86 ppb), and improved stability. The experimental and density functional theory (DFT) studies revealed that the abundant oxygen vacancy sites of Fe2O3 contributed to stabilizing the Pt atoms via electron transfer. In addition, the stabilized Pt atoms also greatly promote the electron transfer of H2 molecules to Fe2O3, thereby achieving an excellent H2 sensing performance. This work provides a potential strategy for the development of highly selective and stable chemical sensors.

Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke.

Objective: To explore the efficacy of ginkgo diterpene lactone (GDLM) on cognitive function in patients with acute ischemic stroke (AIS). Methods: A total of 126 patients with AIS in Shaanxi Provincial People's Hospital from July 2019 to December 2020 were collected and randomly divided into the control group and treatment group (n = 63). All patients received conventional treatment, on which 25 mg/day GDLM was administered in the treatment group. Coagulation and inflammation indexes, National Institutes of Health Stroke Scale (NIHSS) and activities of daily living scale (ADL) scores were measured before and 14 days after treatment. NIHSS and ADL scores were performed again after 3 months. Cognitive function was assessed by Montréal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, and potential P300. Results: After 14 days of treatment, all biochemical indices were lower than before treatment (P < 0.05). The NIHSS and ADL scores of the treatment group were significantly better than those of the control group after treatment (P < 0.05). The MoCA and MMSE scores of the treatment group improved more significantly compared with the control group (P < 0.05). After treatment, the P300 indexes of both groups were significantly better than before treatment (P < 0.05). Conclusion: Conventional treatment of AIS combined with GDLM can effectively improve the cognitive function of patients, which is worthy of clinical recommendation.

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis.

CONTEXT: Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain. OBJECTIVE: To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR). RESULTS: Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively. CONCLUSIONS: The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

A coadapted KNL1 and spindle assembly checkpoint axis orchestrates precise mitosis in Arabidopsis.

The kinetochore scaffold 1 (KNL1) protein recruits spindle assembly checkpoint (SAC) proteins to ensure accurate chromosome segregation during mitosis. Despite such a conserved function among eukaryotic organisms, its molecular architectures have rapidly evolved so that the functional mode of plant KNL1 is largely unknown. To understand how SAC signaling is regulated at kinetochores, we characterized the function of the KNL1 gene in Arabidopsis thaliana. The KNL1 protein was detected at kinetochores throughout the mitotic cell cycle, and null knl1 mutants were viable and fertile but exhibited severe vegetative and reproductive defects. The mutant cells showed serious impairments of chromosome congression and segregation, that resulted in the formation of micronuclei. In the absence of KNL1, core SAC proteins were no longer detected at the kinetochores, and the SAC was not activated by unattached or misaligned chromosomes. Arabidopsis KNL1 interacted with SAC essential proteins BUB3.3 and BMF3 through specific regions that were not found in known KNL1 proteins of other species, and recruited them independently to kinetochores. Furthermore, we demonstrated that upon ectopic expression, the KNL1 homolog from the dicot tomato was able to functionally substitute KNL1 in A. thaliana, while others from the monocot rice or moss associated with kinetochores but were not functional, as reflected by sequence variations of the kinetochore proteins in different plant lineages. Our results brought insights into understanding the rapid evolution and lineage-specific connection between KNL1 and the SAC signaling molecules.

Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report.

Infection following inguinal hernia repair (IHR) is uncommon. Rational use of antibiotics can significantly improve the prognosis of patients. However, accurately identifying the pathogen involved is usually challenging. This case report describes a patient who developed intermittent fever after undergoing open preperitoneal tension-free repair of a bilateral inguinal hernia. The scrotal fluid specimen was cultured and subjected to metagenomic next-generation sequencing (mNGS). Culture revealed the presence of Enterococcus faecalis (a facultative anaerobe). However, mNGS detected E. faecalis along with multiple anaerobic bacteria including Bacteroides thetaiotaomicron, Parabacteroides distasonis, and Levyella massiliensis. The patient was finally diagnosed with a mixed infection of E. faecalis and multiple anaerobes, and his condition was effectively controlled after timely adjustment of the antibiotic regimen. Treating postoperative infections with multiple concurrent conditions can be challenging. mNGS is valuable for the accurate diagnosis and treatment of infections, as it not only can further verify the culture results, but also assist clinicians in ruling out pulmonary infection caused by hematogenous dissemination after IHR in patients.

Association of time spent outdoors with the risk of Parkinson's disease: a prospective cohort study of 329,359 participants.

BACKGROUND: Studies on the association between time spent outdoors and the development of Parkinson's disease (PD) are lacking, and whether this relationship differs in different subgroups (age, sex) remains unclear. OBJECTIVE: We here examined the association between time spent outdoors and the incidence of PD in different seasons. METHODS: This study included 329,359 participants from the UK Biobank. Data regarding hours spent outdoors during a typical day were obtained through questionnaires. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for the association between exposure to outdoors duration and PD incidence. Restricted cubic spline was used to explore the potential nonlinear relationship between time spent outdoors and PD risk. To explore the potential mechanisms of time spent outdoors effecting the risk of PD incidence, their association with serum vitamin D was further analysed separately. RESULTS: During a median follow-up of 13.57 years, 2,238 participants developed PD. In summer, time spent outdoors > 5.0 h/day was associated with a reduced PD risk compared with ≤ 2.0 h/day (HR = 0.84, 95% CI, 0.74-0.95). In winter too, time spent outdoors > 2.0 h/day was also associated with a reduced PD risk compared with ≤ 1.0 h/day (HR = 0.85, 95% CI, 0.76-0.94). For annual average time spent outdoors, participants who went outdoors for more than 3.5 h/day had a reduced PD risk than those who went outdoors for ≤ 1.5 h/day (HR = 0.85, 95% CI, 0.75-0.96). Additionally, sex and age differences were observed in the association between time spent outdoors and the PD risk. Moreover, Time spent outdoors was observed to be positively associated with serum vitamin D levels. Compared with serum vitamin D-deficient participants, the risk of PD was reduced by 15% in the sufficient participants. CONCLUSION: In the total population, higher time spent outdoors was linked to a reduced PD risk. However, this association may vary among different age or sex groups.

Galvanic stabilization of Zn metals for long-life aqueous batteries.

Rechargeable aqueous Zn-ion batteries have received extensive attention due to their environmental friendliness, high safety, and low cost. However, the Zn dendrite growth during plating/stripping cycles, which deteriorates coulombic efficiency and shortens the cycle life, dramatically hinders the application of Zn anodes in batteries. Herein, we propose to grow an In layer on Zn foils through spontaneous Galvanic reaction to address the challenging Zn dendrites.In-situoptical observations show that this strategy effectively suppresses the dendrite growth, thereby leading to a robust and stable Zn metal anode with low voltage hysteresis (30 mV at 0.4 mA·cm-2) and long cycle life of over 1200 h in symmetric cells. Meanwhile, the full cell assembled with the modified Zn anode and MnO2cathode exhibits excellent cycling performance over 2000 cycles and a high discharge capacity of 89.1 mAh·g-1. This work provides an efficient pathway for interfacial engineering towards stable Zn anodes.

The association between plain water intake and periodontitis in the population aged over 45: a cross-sectional study based on NHANES 2009-2014.

BACKGROUND: Numerous studies have demonstrated the impact of beverage consumption on overall health and oral health. Specifically, high consumption of sugar-sweetened beverages and coffee has been associated with an increased risk of metabolic disorders and periodontitis. Conversely, high intake of plain water has been linked to various health benefits, including weight management and reduced energy intake. However, no previous studies have explored the potential association between plain water intake and the risk of periodontitis. OBJECTIVES: Our objective was to investigate the relationship between plain water consumption and periodontitis in a middle-aged and elderly population. METHODS: The present cross-sectional study was conducted among participants aged ≥ 45 in the 2009-2014 National Health and Nutrition Examination Surveys. Multivariable regression analysis, subgroup analysis and smooth fitting tests were conducted to explore the independent relationship between plain water intake and periodontitis. RESULTS: A total of 5,882 participants were enrolled,62.02% have periodontitis. Periodontitis patients have lower plain water intake. The multivariable regression tests showed that the risk of periodontitis decreased with increased plain water intake quartiles (Q4 OR = 0.78; 95%CI 0.62-0.96) after fully adjustment. Subgroup analysis and interaction tests showed that gender, age, smoking, diabetes, hypertension or BMI does not significantly interact with the association. However, the relation was significant in males (Q4 OR = 0.64; 95%CI 0.47-0.86) but not in females (Q4 OR = 0.97;95% CI 0.71-1.31). In the smoothed curve fits stratified by gender, the curve for male participants displayed as a U-shape, with an optimal plain water intake at 1200 ml/day. For males drinking plain water less than 1200 ml/day, the risk of periodontitis decreased by 24% with each increase of 500 ml plain water intake (OR = 0.76, 95%CI 0.66-0.87, p < 0.001). CONCLUSIONS: Together, the results showed that plain water intake is negatively associated with periodontitis risk in US middle aged and elderly population. Further studies are needed to investigate the mechanism unites this association. Attention should be given to adequate plain water intake when considering dietary suggestions to the population at high risk of developing periodontitis, especially for men.

Electronic Modulation of MoS2 Nanosheets by N-Doping for Highly Sensitive NO2 Detection at Room Temperature.

Transition metal dichalcogenide (TMD) materials hold great promise for gas sensors working at room temperature (RT). But the low response and slow dynamics derived from pristine TMDs remain a challenge toward their real applications. In this work, we report an efficient N-doping strategy to modulate the electronic structure of MoS2 nanosheets (N-MoS2) to achieve improved detection toward NO2. The effect of N-doping on the sensor properties, which has been rarely investigated, is elucidated by both experimental and computational studies. Due to N-doping, the Fermi level of N-MoS2 decreased from -5.29 to -5.33 eV and the band gap was reduced from 1.79 to 1.65 eV. The smaller band gap indicated the reduced resistance of N-MoS2 compared to that of original MoS2. As a result, the response of the MoS2 sensor to 10 ppm of NO2 was improved from 1.23 to 2.31 at RT. The sensor also has a limit of detection (LOD) of 62.5 ppb. To explain the effect of N-doping, density functional theory (DFT) calculations were conducted to figure out the important roles played by N-doping. This work demonstrates a pathway to modulate the chemical and electronic structures of TMD materials for advanced sensors.

An Analysis and Literature Review of a Family Case of Acute Intermittent Porphyria With Initial Symptoms of Epileptic Seizure.

Acute intermittent porphyria (AIP) is the most common form of acute porphyria and is characterized by acute onset and recurrent episodes. Clinical presentation frequently initiates with gastrointestinal symptoms and is often misdiagnosed or delayed secondary to nonspecific symptoms. Acute porphyria with epilepsy as the primary symptom is a very unusual or unexpected manifestation. This family case found an unexpected association between acute porphyria and seizures. This patient is a 33-year-old woman whose initial symptom was symptomatic epilepsy, followed by significant abdominal pain. After excluding infection, immunity, and other factors, whole exome sequencing analysis showed the presence of c.22dupG mutation in the HMBS gene and the patient was finally diagnosed with AIP. Her symptoms significantly improved after receiving high-glucose and high-carbohydrate load treatment. This case report is rare and suggests that for patients who experience epileptic seizures coupled with complaints related to the abdomen, the possibility of porphyria should be specially considered in the differential diagnosis.

Circular RNA PARG adjusts miR-140-3p to influence progression in sepsis.

Sepsis has been characterized as a frequent medical problem with high mortality and severe complication medical problem in the intensive care unit (ICU). Here, qRT-PCR was used to examine circRNA PARG expression levels in patients with sepsis and in human pulmonary microvascular endothelial cells (HPMEC). Lipopolysaccharide (LPS)-simulated HPMEC were hybridized using RNA-Fluorescence in situ hybridization to confirm the location of circRNA PARG and miR-140-3p. The biological role of downregulated circRNA PARGin cellular proliferation, apoptosis, and inflammatory and apoptosis responses was evaluated. performed A dual-luciferase reporter assay was performed to determine the relationship between the circRNA PARG with miR-140-3p. In this study,circRNA PARG aberrant expression was found, and the effects of circRNA PARG on lipopolysaccharide (LPS)-stimulated apoptosis of HPMEC cells were further investigated. Down-regulated circRNA PARG led to significant alleviation of LPS-simulated cell apoptosis via inhibition of inflammatory and apoptosis-related genes, while upregulated circRNA PARG exhibited the opposite effects. Further findings indicated that circRNA PARG positively modulated the relative level of miR-140-3p, which has been confirmed using the luciferase reporter assay. Upregulated circRNA PARG led to a reversal of LPS-simulated cells after transfection of miR-140-3p mimic. In general, a novel insight into understanding the important effects of circRNA PARG in sepsis is provided.

Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing.

Clinical presentation of central nervous system (CNS) infections caused by varicella-zoster virus (VZV) is highly sophisticated, making identification challenging. We retrospectively reported 18 cases of VZV neurologic disease confirmed by metagenomic next-generation sequencing (mNGS). The detection rate of mNGS was higher than that of PCR assay (100 vs 66.7%, p < 0.05) and serum IgM antibody (100 vs 68.8%, p < 0.05) measurement. Of the 18 cases, five patients were diagnosed with acute meningitis, three with acute meningitis combined with facial neuritis, three with acute meningitis combined with polycranial neuritis, and the remaining seven with various clinical diagnoses. Typical clinical symptoms included headache (15), fever (9), and rash (11). Cranial or spinal MRI showed abnormalities in 12 patients, and 17 patients had obvious neurological symptoms. The predominant genotype of VZV in this study was genotype J (100%, 10/10). All patients were treated with acyclovir/penciclovir and dexamethasone, 16 recovered and 2 died. Our study highlights the good performance of mNGS in diagnosing CNS infection caused by VZV. It could provide additional diagnostic evidence in patients with diverse clinical spectrum and variable manifestations.

A case report of brainstem hemorrhage due to Rhizopus delemar-induced encephalitis diagnosed by metagenomic next-generation sequencing (mNGS).

BACKGROUND: Rhizopus delemar is an invasive fungal pathogen that can cause fatal mucormycosis in immunodeficient individuals. Encephalitis caused by R. delemar is rare and difficult to diagnose early. Clinical detection methods for R. delemar include blood fungal culture, direct microscopic examination, and histopathological examination, but the detection is often inadequate for clinical diagnosis and can easily lead to missed diagnosis with delayed treatment. CASE PRESENTATION: We report a case of a 47-year-old male with brainstem hemorrhage caused by encephalitis due to R. delemar. The patient had a history of hypertension, type 2 diabetes, and irregular medication. No pathogens were detected in cerebrospinal fluid (CSF) and nasopharyngeal secretion cultures. R. delemar was identified by metagenomic next-generation sequencing (mNGS) in CSF, and in combination with the patient's clinical characteristics, encephalitis caused by R. delemar was diagnosed. Antibiotic treatment using amphotericin B liposome in combination with posaconazole was given immediately. However, due to progressive aggravation of the patient's symptoms, he later died due to brainstem hemorrhage after giving up treatment. CONCLUSIONS: mNGS technique is a potential approach for the early diagnosis of infections, which can help clinicians provide appropriate antibiotic treatments, thus reducing the mortality and disability rate of patients.