Flux Crystal Growth, Structure, and Optical Properties of LiLa3Ti2S3O6: An Oxysulfide Phase Derived from K2NiF4-Type Structure.

Single crystals of a new titanium oxysulfide, LiLa3Ti2S3O6, were grown from a KI molten salt. Single-crystal X-ray diffraction analysis revealed that LiLa3Ti2S3O6 crystallizes in the space group Pnma with lattice parameters of a = 11.7319(4) Å, b = 3.94787(14) Å, and c = 20.6885(6) Å. In this structure, the one-dimensional chains of corner-sharing TiO5S octahedra are further corner-linked via equatorial and apical oxygen atoms to form unique corrugated two-dimensional perovskite-type layers in the ab plane with one octahedral thickness. These layers were intervened along the c-axis by the LaS rock-salt layers corrugated concomitantly with the perovskite-type layers, and LiO2S2 tetrahedral chains were located between these two types of two-dimensional layers. LiLa3Ti2S3O6 can be viewed as a modified K2NiF4-type structure with TiO5S octahedral layers stacked in a zigzag manner along the c axis. The oxysulfide has a direct-type band gap of 1.85 eV, based on UV-vis-NIR diffuse reflectance measurements. First-principles calculations showed that the conduction band minimum mainly consists of Ti 3d orbitals, and the valence band maximum consists of S 3p, O 2p, and Li 2s orbitals. The electronic structures near the Fermi level are similar to those of the structurally related photocatalytic oxysulfides Y2Ti2S2O5 and La5Ti2CuS5O7.

Customizable Colorimetric Sensor Array via a High-Throughput Robot for Mitigation of Humidity Interference in Gas Sensing.

One challenge for gas sensors is humidity interference, as dynamic humidity conditions can cause unpredictable fluctuations in the response signal to analytes, increasing quantitative detection errors. Here, we introduce a concept: Select humidity sensors from a pool to compensate for the humidity signal for each gas sensor. In contrast to traditional methods that extremely suppress the humidity response, the sensor pool allows for more accurate gas quantification across a broader range of application scenarios by supplying customized, high-dimensional humidity response data as extrinsic compensation. As a proof-of-concept, mitigation of humidity interference in colorimetric gas quantification was achieved in three steps. First, across a ten-dimensional variable space, an algorithm-driven high-throughput experimental robot discovered multiple local optimum regions where colorimetric humidity sensing formulations exhibited high evaluations on sensitivity, reversibility, response time, and color change extent for 10-90% relative humidity (RH) in room temperature (25 °C). Second, from the local optimum regions, 91 sensing formulations with diverse variables were selected to construct a parent colorimetric humidity sensor array as the sensor pool for humidity signal compensation. Third, the quasi-optimal sensor subarrays were identified as customized humidity signal compensation solutions for different gas sensing scenarios across an approximately full dynamic range of humidity (10-90% RH) using an ingenious combination optimization strategy, and two accurate quantitative detections were attained: one with a mean absolute percentage error (MAPE) reduction from 4.4 to 0.75% and the other from 5.48 to 1.37%. Moreover, the parent sensor array's excellent humidity selectivity was validated against 10 gases. This work demonstrates the feasibility and superiority of robot-assisted construction of a customizable parent colorimetric sensor array to mitigate humidity interference in gas quantification.

Comparison of sensitivity between blood parameters and a genotoxic biomarker at low blood Pb levels: A population-based study.

BACKGROUND: Previous studies reported that lead (Pb) exposure induced adverse health effects at high exposure concentrations, however, there have been limited data on sensitivity comparisons among different health outcomes at low blood Pb levels. OBJECTIVES: To compare sensitivity between blood parameters and a genotoxic biomarker among workers exposed to low blood Pb levels (< 20 µg/dl), and to estimate a benchmark dose (BMD). METHODS: Pb-exposed workers were recruited from a lead-acid storage battery plant. Their blood lead levels (BLLs) were measured. Blood parameters and micronuclei (MN) frequencies were determined. Multivariate linear or Poisson regression was used to analyze relationships between blood parameters or MN frequencies with BLLs. Two BMD software were used to calculate BMD and its 95 % lower confidence limit (BMDL) for BLLs. RESULTS: The median BLL for 611 workers was 10.44 µg/dl with the 25th and 75th percentile being 7.37 and 14.62 µg/dl among all participants. There were significantly negative correlations between blood parameters and BLLs. However, MN frequencies correlated positively with BLLs (all P<0.05). Results from the two BMD software revealed that the dichotomous model was superior to the continuous model, and the BMDL for BLL derived from red blood cell (RBC) was 15.11 µg/dl, from hemoglobin (HGB) was 8.50 µg/dl, from mean corpuscular hemoglobin (MCH) was 7.87 µg/dl, from mean corpuscular hemoglobin concentration (MCHC) was 3.98 µg/dl, from mean corpuscular volume (MCV) was 11.44 µg/dl, and from hematocrit (HCT) was 6.65 µg/dl. The conservative BMDL obtained from the MN data was 7.52 µg/dl. CONCLUSION: Our study shows that low dose Pb exposure caused decrease of blood parameters and increase of MN frequencies. The genotoxic biomarker was more sensitive than most blood parameters. BMDLs for BLL derived from MN frequencies and the red blood cell indicators should be considered as new occupational exposure limits. Our results suggest that MN assay can be considered as a part of occupational health examination items.

Gabapentin alleviates peripheral nerve sensitization induced by inflammatory arthritis via ionotropic glutamate receptor NR2B subunit.

Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE2), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca2+. Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis.

Thoracoscopic wedge resection of the upper lobe of the left lung achieved by a new approach of laryngeal mask general anesthesia with preservation of spontaneous breathing: A case report.

INTRODUCTION: General laryngeal mask anesthesia with the preservation of spontaneous breathing has accelerated the advancement of the enhanced recovery after surgery concept in thoracoscopic surgery. However, the need for increased doses of anesthetic drugs to reduce laryngeal mask airway (LMA) stimulation poses challenges due to the increased risk of hypotension, respiratory depression, susceptibility to hypoxemia, and carbon dioxide retention, particularly in the lateral position. PATIENT CONCERNS: During the perioperative period, reducing the dose of anesthetic drugs while simultaneously improving LMA tolerance and preventing circulatory and respiratory depression poses a challenge. DIAGNOSES: The patient was diagnosed with a nodule in the upper lobe of the left lung. INTERVENTIONS: In this case, we chose remimazolam sedation, which mildly inhibits circulatory respiration, and used mucosal surface anesthesia in the pharynx. This approach improved the patient's tolerance to LMA, reduced the dose of anesthetic drugs, and facilitated the successful thoracoscopic wedge resection of the upper lobe of the left lung with preservation of spontaneous respiration. OUTCOMES: During 2 weeks follow-up, the patient recovered satisfactorily and did not report any discomfort. CONCLUSION: We used pharyngeal mucosal surface anesthesia and thoracic paravertebral nerve block in combination with remimazolam sedation to provide precise analgesia, moderate sedation, and successful LMA general anesthesia with preservation of spontaneous respiration in patients undergoing thoracoscopic pulmonary wedge resection.

Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity.

The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.

A Prediction Model for Assessing the Efficacy of Thermal Ablation in Treating Benign Thyroid Nodules ≥ 2 cm: A Multi-Center Retrospective Study.

OBJECTIVES: To develop and validate a prediction model utilizing clinical and ultrasound (US) data for preoperative assessment of efficacy following US-guided thermal ablation (TA) in patients with benign thyroid nodules (BTNs) ≥ 2 cm. MATERIALS AND METHODS: We retrospectively assessed 962 patients with 1011 BTNs who underwent TA at four tertiary centers between May 2018 and July 2022. Ablation efficacy was categorized into therapeutic success (volume reduction rate [VRR] > 50%) and non-therapeutic success (VRR ≤ 50%). We identified independent factors influencing the ablation efficacy of BTNs ≥ 2 cm in the training set using multivariate logistic regression. On this basis, a prediction model was established. The performance of model was further evaluated by discrimination (area under the curve [AUC]) in the validation set. RESULTS: Of the 1011 nodules included, 952 (94.2%) achieved therapeutic success at the 12-month follow-up after TA. Independent factors influencing VRR > 50% included sex, nodular composition, calcification, volume, and largest diameter (all p < 0.05). The prediction equation was established as follows: p = 1/1 + Exp∑[8.113 -2.720 × (if predominantly solid) -2.790 × (if solid) -1.275 × (if 10 mL < volume ≤ 30mL) -1.743 × (if volume > 30 mL) -1.268 × (if with calcification) -2.859 × (if largest diameter > 3 cm) +1.143 × (if female)]. This model showed great discrimination, with AUC of 0.908 (95% confidence interval [CI]: 0.868-0.947) and 0.850 (95% CI: 0.748-0.952) in the training and validation sets, respectively. CONCLUSIONS: A clinical prediction model was successfully developed to preoperatively predict the therapeutic success of BTNs larger than 2 cm in size following US-guided TA. This model aids physicians in evaluating treatment efficacy and devising personalized prognostic plans.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Here, we quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR: 1.66; 95% CI: 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

NMR-Guided Isolation of Anti-inflammatory Carabranolides from the Fruits of Carpesium abrotanoides L.

Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1-11), along with five known ones (12-16), were isolated from the fruits of Carpesium abrotanoides L. Compounds 1-11 are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2-4, 15, and 16 exhibited significant inhibitory activity against LPS-induced NO release with an IC50 value of 5.6-9.1 µM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.

A novel nomogram model for lung adenocarcinoma subtypes based on RNA-modification regulatory genes.

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research. Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways. Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

Systematic review of the mechanism and assessment of liver fibrosis in biliary atresia.

PURPOSE: This study systematically reviewed our team's research on the mechanism and assessment of liver fibrosis in BA, summarized our experience, and discussed the future development direction. METHODS: In this study, Pubmed and Wanfang databases were searched to collect the literature published by our team on the mechanisms of liver fibrosis in BA and the assessment of liver fibrosis in BA, and the above research results were systematically reviewed. RESULTS: A total of 58 articles were retrieved. Among the included articles, 25 articles related to the mechanism of liver fibrosis in BA, and five articles evaluated liver fibrosis in BA. This article introduces the key pathways and molecules of liver fibrosis in BA and proposes a new grading system for liver fibrosis in BA. CONCLUSIONS: The new BA liver fibrosis grading method is expected to assess children's conditions, guide treatment, and improve prognosis more accurately. In addition, we believe that the TGF-ß1 signaling pathway is the most important in the study of liver fibrosis in BA, and at the same time, the study of EMT occurrence in BA should also be deepened to resolve the controversy on this issue.

Successful use of remimazolam combined with remifentanil for painless gastroscopy in a patient with morbid obesity: a case report.

Backgroud: In recent years, as the number of people with obesity has surged, the number of morbidly obese patients has also grown. The pathophysiological changes in morbid obesity can lead to combined lung diseases, which may result in hypoventilation, hypoxemia, acute upper airway obstruction, acute respiratory distress syndrome, and sleep apnea syndrome, posing serious challenges to anesthesia management. Here, we describe a case of the administration of remimazolam combined with remifentanil in a patient with morbid obesity undergoing gastroscopy. This has rarely been reported in clinical practice, and we present our management experience here with the aim of providing a reference for clinical work. Case presentation: We report the case of a 32-year-old male hypertensive patient with a height of 180 cm, weight of 145 kg, and body mass index of 44.8 kg/m2. The patient's main complaint was intermittent hunger pain for more than 1 year, and duodenal polyps were found. Considering the patient's morbid obesity and the combination of sleep apnea syndrome and hypertension, we administered remimazolam along with remifentanil to ensure perioperative safety. Conclusion: The procedure lasted 30 min, and the anesthesia was satisfactory with no complications. Remimazolam combined with remifentanil intravenous anesthesia is safe for short gastroscopy in patients with morbidly obesity. The administration of a small dose of split-titration delivery facilitates the maintenance of stable vital signs.

Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study.

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

Palmitoylation of NLRP3 Modulates Inflammasome Activation and Inflammatory Bowel Disease Development.

Aberrant activity of NLRP3 has been shown associations with severe diseases. Palmitoylation is a kind of protein post-translational modification, which has been shown to regulate cancer development and the innate immune system. Here, we showed that NLRP3 is palmitoylated at Cys419 and that palmitoyltransferase ZDHHC17 is the predominant enzyme that mediates NLRP3 palmitoylation and promotes NLRP3 activation by interacting with NLRP3 and facilitating NIMA-related kinase 7 (NEK7)-NLRP3 interactions. Blockade of NLRP3 palmitoylation by a palmitoylation inhibitor, 2-bromopalmitate, effectively inhibited NLRP3 activation in vitro. Also, in a dextran sulfate sodium-induced colitis model in mice, 2-bromopalmitate application could attenuate weight loss, improve the survival rate, and rescue pathological changes in the colon of mice. Overall, our study reveals that palmitoylation of NLPR3 modulates inflammasome activation and inflammatory bowel disease development. We propose that drugs targeting NLRP3 palmitoylation could be promising candidates in the treatment of NLRP3-mediated inflammatory diseases.

Molecular and therapeutic landscape of ferroptosis in skin diseases.

ABSTRACT: Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis's role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

The Influence of Climate Change on the Distribution of Hibiscus mutabilis in China: MaxEnt Model-Based Prediction.

Our study utilized 374 geographical distribution records of H. mutabilis and 19 bioclimatic factors, employing the MaxEnt model and the Geographic Information System (ArcGIS). The key environmental variables influencing the suitable distribution areas of H. mutabilis were analyzed through the comprehensive contribution rate, permutation importance, and Pearson correlation coefficient. Based on this analysis, the contemporary and future suitable distribution areas and their extents were predicted. The results indicate that the key limiting factor affecting the suitable distribution areas of H. mutabilis is the precipitation of the driest month (bio14), with secondary factors being annual precipitation (bio12), annual mean temperature (bio1), and annual temperature range (bio7). Under contemporary climate conditions, the total suitable area for H. mutabilis is approximately 2,076,600 km2, primarily concentrated in the tropical and subtropical regions of southeastern China. Under low-to-medium-emission scenarios (SSP1-2.6, SSP2-4.5), the total suitable area of H. mutabilis shows a trend of first decreasing and then increasing compared to the current scenario. In contrast, under high-emission scenarios (SSP5-8.5), it exhibits a trend of first increasing and then decreasing. The spatial pattern changes indicate that the retention rate of suitable areas for H. mutabilis ranges from 95.28% to 99.28%, with the distribution centers primarily located in Hunan and Guizhou provinces, showing an overall migration trend towards the west and north. These findings suggest that H. mutabilis possesses a certain level of adaptability to climate change. However, it is crucial to consider regional drought and sudden drought events in practical cultivation and introduction processes. The results of our study provide a scientific basis for the rational cultivation management, conservation, and utilization of germplasm resources of H. mutabilis.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients: A prospective, Multicenter cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

Pharmacological mTOR inhibitors in ameliorating Alzheimer's disease: current review and perspectives.

Traditionally, pharmacological mammalian/mechanistic targets of rapamycin (mTOR) kinase inhibitors have been used during transplantation and tumor treatment. Emerging pre-clinical evidence from the last decade displayed the surprising effectiveness of mTOR inhibitors in ameliorating Alzheimer's Disease (AD), a common neurodegenerative disorder characterized by progressive cognitive function decline and memory loss. Research shows mTOR activation as an early event in AD development, and inhibiting mTOR may promote the resolution of many hallmarks of Alzheimer's. Aberrant protein aggregation, including amyloid-beta (Aß) deposition and tau filaments, and cognitive defects, are reversed upon mTOR inhibition. A closer inspection of the evidence highlighted a temporal dependence and a hallmark-specific nature of such beneficial effects. Time of administration relative to disease progression, and a maintenance of a functional lysosomal system, could modulate its effectiveness. Moreover, mTOR inhibition also exerts distinct effects between neurons, glial cells, and endothelial cells. Different pharmacological properties of the inhibitors also produce different effects based on different blood-brain barrier (BBB) entry capacities and mTOR inhibition sites. This questions the effectiveness of mTOR inhibition as a viable AD intervention strategy. In this review, we first summarize the different mTOR inhibitors available and their characteristics. We then comprehensively update and discuss the pre-clinical results of mTOR inhibition to resolve many of the hallmarks of AD. Key pathologies discussed include Aß deposition, tauopathies, aberrant neuroinflammation, and neurovascular system breakdowns.