The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial.

The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 µg·kg-1·h-1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 µg·kg-1·h-1 (95% CI: .29-.35) and .48 µg·kg-1·h-1 (95% CI: .44-.56), respectively. Probit(p) = -2.84 + 9.28 × ln (Dose), (χ2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

MK-BMC: a Multi-Kernel framework with Boosted distance metrics for Microbiome data for Classification.

MOTIVATION: Research on human microbiome has suggested associations with human health, opening opportunities to predict health outcomes using microbiome. Studies have also suggested that diverse forms of taxa such as rare taxa that are evolutionally related and abundant taxa that are evolutionally unrelated could be associated with or predictive of a health outcome. Although prediction models were developed for microbiome data, no prediction models currently exist that use multiple forms of microbiome-outcome associations. RESULTS: We developed MK-BMC, a Multi-Kernel framework with Boosted distance Metrics for Classification using microbiome data. We propose to first boost widely used distance metrics for microbiome data using taxon-level association signal strengths to up-weight taxa that are potentially associated with an outcome of interest. We then propose a multi-kernel prediction model with one kernel capturing one form of association between taxa and the outcome, where a kernel measures similarities of microbiome compositions between pairs of samples being transformed from a proposed boosted distance metric. We demonstrated superior prediction performance of (i) boosted distance metrics for microbiome data over original ones and (ii) MK-BMC over competing methods through extensive simulations. We applied MK-BMC to predict thyroid, obesity, and inflammatory bowel disease status using gut microbiome data from the American Gut Project and observed much-improved prediction performance over that of competing methods. The learned kernel weights help us understand contributions of individual microbiome signal forms nicely. AVAILABILITY AND IMPLEMENTATION: Source code together with a sample input dataset is available at https://github.com/HXu06/MK-BMC.

4,8-Dicarboxyl-8,9-iridoid-1-glycoside inhibits apoptosis in human osteoarthritis chondrocytes via enhanced c-MYC-mediated cholesterol metabolism in vitro.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease related to cholesterol metabolism disorders. However, current therapies for OA are insufficient and no convincing disease-modifying OA drugs exist. Therefore, we aimed to elucidate the mechanism by which borojoa iridoid glycoside (BIG) inhibits chondrocyte apoptosis in OA. METHODS: Borojoa pulp was heated to 70 °C, and the main active substance in borojoa, BIG, was extracted by fractionation at an ultraviolet 254-nm absorption peak. Chondrocytes were identified by immunohistochemistry and visualized by immunofluorescence confocal microscopy. The proliferation of chondrocytes cultured with BIG was determined by MTS assay. The apoptosis of chondrocytes cultured with BIG was tested by Annexin V-FITC/PI, and the cytokine, protein, and cholesterol levels in chondrocytes were detected by ELISA, RT‒qPCR, Western blot, and biochemistry analyses. Protein‒protein interactions were verified by a coimmunoprecipitation (Co-IP) assay. RESULTS: BIG promoted chondrocyte proliferation and reduced apoptosis in vitro. BIG induced an alteration of the total RNA profiles in chondrocytes, and bioinformatic analysis showed that BIG inhibited chondrocyte apoptosis by promoting c-MYC expression; KEGG analysis confirmed that BIG-inhibited apoptosis was enriched in the cell cycle pathway. Flow cell cycle experiments confirmed that BIG promoted chondrocyte proliferation by significantly increasing the S phase cell number. The c-MYC inhibitor 10058-F4 stimulated the increased expression of IL-1ß, IL-6, TNF-α, and AGEs and suppressed the cholesterol metabolism, which promoted chondrocyte apoptosis and autophagy. Co-IP analysis showed that BIG promoted the interaction of c-MYC and CH25H, Bcl-2, which suggests that BIG could inhibit chondrocyte apoptosis in part by enhancing c-MYC-mediated cholesterol metabolism. CONCLUSIONS: This study confirmed that BIG promotes chondrocyte proliferation and inhibits apoptosis and autophagy, and BIG improving OA is associated with cholesterol metabolism. The results identify a potential mechanism by which BIG enhances c-MYC-mediated CH25H regulation of cholesterol metabolism in vitro and suggest that BIG might be a promising new drug against OA.

Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis.

Palmitoyl protein thioesterase 1(PPT1) is a lysosomal enzyme that catalyzes the protein depalmitoylation. It is considered to play a crucial role in regulating lysosomes, mitochondria and lipid metabolism. PPT1 has been reported to play an important role in the occurrence and progression of diseases, such as neurological diseases and cancers. However, the regulatory mechanisms remain unknown. In this review, we summarize the progress of PPT1 function and mechanisms in neurological disorders and cancers, which will provide as reference and guidance for exploring the regulatory mechanisms of PPT1 and developing new drugs for treating related diseases in the future.

An emerging research: the role of hepatocellular carcinoma-derived exosomal circRNAs in the immune microenvironment.

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is one of the leading causes of cancer-related death and is associated with a poor prognosis. The tumor microenvironment (TME) of HCC comprises immune, immunosuppressive, and interstitial cells with hypoxic, angiogenic, metabolic reprogramming, inflammatory, and immunosuppressive features. Exosomes are nanoscale extracellular vesicles that secrete biologically active signaling molecules such as deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), microribonucleic acid (miRNA), proteins, and lipids. These signaling molecules act as messengers in the tumor microenvironment, especially the tumor immunosuppressive microenvironment. Exosomal circRNAs reshape the tumor microenvironment by prompting hypoxic stress response, stimulating angiogenesis, contributing to metabolic reprogramming, facilitating inflammatory changes in the HCC cells and inducing tumor immunosuppression. The exosomes secreted by HCC cells carry circRNA into immune cells, which intervene in the activation of immune cells and promote the overexpression of immune checkpoints to regulate immune response, leading tumor cells to acquire immunosuppressive properties. Furthermore, immunosuppression is the final result of a combination of TME-related factors, including hypoxia, angiogenesis, metabolic reprogramming, and inflammation changes. In conclusion, exosomal circRNA accelerates the tumor progression by adjusting the phenotype of the tumor microenvironment and ultimately forming an immunosuppressive microenvironment. HCC-derived exosomal circRNA can affect HCC cell proliferation, invasion, metastasis, and induction of chemoresistance. Therefore, this review aimed to summarize the composition and function of these exosomes, the role that HCC-derived exosomal circRNAs play in microenvironment formation, and the interactions between exosomes and immune cells. This review outlines the role of exosomal circRNAs in the malignant phenotype of HCC and provides a preliminary exploration of the clinical utility of exosomal circRNAs.

Improving self-directed learning ability of medical students using the blended teaching method: a quasi-experimental study.

BACKGROUND: Self-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students' SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching. METHODS: This study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods. RESULTS: At the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG. CONCLUSION: The blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students' SDL abilities.

DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells.

(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA-miRNA-mRNA regulatory networks, 275 groups of circRNA-miRNA-mRNA regulatory networks, and five groups of lncRNA/circRNA-miRNA-mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.

Factors Associated with Large Renal Function Decline in Patients with Chronic Hepatitis C Successfully Treated with Direct-Acting Antiviral Therapy.

The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m2, respectively (p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010-2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007-1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342-0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication.

Functional connectivity and structural changes of thalamic subregions in episodic migraine.

BACKGROUND: The thalamus plays a crucial role in transmitting nociceptive information to various cortical regions involving migraine-related allodynia and photophobia. Abnormal structural and functional alterations related to the thalamus have been well established. However, it is unknown whether the brain structure and function of the thalamic subregions are differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing the structure and function of 16 thalamic subregions between patients with episodic migraine (EM) and healthy controls (HCs). METHODS: Twenty-seven patients with EM and 30 sex-, age- and education-matched HCs underwent resting-state functional and structural magnetic resonance imaging scans. Functional connectivity (rsFC), grey matter volume (GMV), and diffusion tensor imaging (DTI) parameters of each subregion of the thalamus were calculated and compared between the two groups. Furthermore, correlation analyses between neuroimaging changes and clinical features were performed in this study. RESULTS: First, compared with HCs, patients with EM exhibited decreased rsFC between the anterior-medial-posterior subregions of the thalamus and brain regions mainly involved in the medial system of the pain processing pathway and default mode network (DMN). Second, for the whole thalamus and each of its subregions, there were no significant differences in GMV between patients with EM and HCs (P > 0.05, Bonferroni corrected). Third, there was no significant difference in DTI parameters between the two groups (P > 0.05). Finally, decreased rsFC was closely related to scores on the Hamilton Rating Scale for Anxiety (HAMA) and Big Five Inventory (BFI) scales. CONCLUSION: Selective functional hypoconnectivity in the thalamic subregions provides neuroimaging evidence supporting the important role of thalamocortical pathway dysfunction in episodic migraine, specifically, that it may modulate emotion and different personality traits in migraine patients.

Determination of the median effective dose of sufentanil for inhibiting the laryngeal mask insertion response in geriatric patients: a prospective, double-blinded, dose-response trial.

BACKGROUND: Laryngeal mask airway(LMA) have been widely used in clinical practice. Irritation to the patient during the insertion of a laryngeal mask can cause hemodynamic fluctuations, which is particularly unsafe for geriatric patients. We used probit regression analysis to determine the median effective dose of sufentanil to inhibit the response to LMA insertion in geriatric patients. METHODS: A total of 90 patients were selected for the study using the following inclusion criteria: age ≥ 65 years old, ASA grade I-III, and scheduled to undergo intravenous general anesthesia with LMA insertion. Each patient received a dose of sufentanil for anesthesia induction in one of six levels: 0.05, 0.1, 0.15, 0.2, 0.25, or 0.3 µg kg-1. LMA insertion was scored with a 3-point, 6-category scale, with scores ≥ 16 indicating effective LMA insertion, and < 16 indicating ineffective LMA insertion. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded 1 min before induction (T1), 1 min after induction (T2), 1 min after LMA insertion (T3), and 5 min after LMA insertion (T4) in each group. In addition, the plasma norepinephrine (NE) levels and adverse reactions were measured at T2 and T3 in each dosage group. RESULTS: Probit regression analysis showed that the ED50 of sufentanil inhibiting the response to LMA insertion in geriatric patients was 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1), and the ED95 was 0.31 µg kg-1 (95% CI: 0.27-0.38 µg kg-1), and the probit(p) = -2.34 + 12.90 × ln(Dose)([Formula: see text] = 0.725, p = 0.948). Among all the patients, the number of effective LMA insertions was 57 (group A), and the number of ineffective LMA insertions was 33 (group B). The MAP, HR, and NE in group B were significantly higher than in group A at T3. CONCLUSIONS: Sufentanil can effectively inhibit the patient's response to LMA insertion, with stable hemodynamics and small stress response. The ED50 and ED95 were 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1) and 0.31 µg kg-1(95% CI: 0.27-0.38 µg kg-1), respectively. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100051827 ) on October 6, 2021.

Dip-Coating Self-Assembly Fabrication and Polarization Sensitive Photoresponse of Aligned Single-Walled Carbon Nanotube Film.

It is challenging to obtain wafer-scaled aligned films for completely exploiting the promising properties of semiconducting single-walled carbon nanotubes (s-SWCNTs). Aligned s-SWCNTs with a large area can be obtained by combining water evaporation and slow withdrawal-induced self-assembly in a dip-coating process. Moreover, the tunability of deposition morphology parameters such as stripe width and spacing is examined. The polarized Raman results show that s-SWCNTs can be aligned in ±8.6°. The derived two terminal photodetector shows both a high negative responsivity of 41 A/W at 520 nm and high polarization sensitivity. Our results indicate that aligned films with a large area may be useful to electronics- and optoelectronics-related applications.

Missed opportunities for screening congenital syphilis early during pregnancy: A case report and brief literature review.

Congenital syphilis is a significant public health problem. Pregnant women infected with Treponema pallidum present with various clinical manifestations, mainly including skin or visceral manifestations. The extensive clinical manifestations of T. pallidum infection mimic those of many other diseases during pregnancy, which may lead to delayed diagnosis and serious consequences. We report a case of fetal T. pallidum infection and premature delivery in a woman whose syphilis screening was negative at 16 weeks of gestation. Despite presenting to the dermatologist at 24 weeks of gestation with maculopapular rash which is usually associated with secondary syphilis, the diagnosis of syphilis was not considered. This case shows that even if early syphilis screening of pregnant women is negative, they may still get infected with T. pallidum later on in pregnancy. Therefore, in patients presenting with a rash without an obvious cause, T. pallidum infection should be excluded. The health status of patients' spouses should be assessed during pregnancy. Additionally, perinatal health education is necessary for women and their spouses during pregnancy. The abovementioned factors could reduce the probability of T. pallidum infection in pregnant women and their infants.

ADT-OH inhibits malignant melanoma metastasis in mice via suppressing CSE/CBS and FAK/Paxillin signaling pathway.

Hydrogen sulfide (H2S) is widely recognized as the third endogenous gas signaling molecule and may play a key role in cancer biological processes. ADT-OH (5-(4-hydroxyphenyl)-3H-1,2-dithiocyclopentene-3-thione) is one of the most widely used organic donors for the slow release of H2S and considered to be a potential anticancer compound. In this study, we investigated the antimetastatic effects of ADT-OH in highly metastatic melanoma cells. A tail-vein-metastasis model was established by injecting B16F10 and A375 cells into the tail veins of mice, whereas a mouse footpad-injection model was established by injecting B16F10 cells into mouse footpads. We showed that administration of ADT-OH significantly inhibited the migration and invasion of melanoma cells in the three different animal models. We further showed that ADT-OH dose-dependently inhibited the migration and invasion of B16F10, B16F1 and A375 melanoma cells as evaluated by wound healing and Transwell assays in vitro. LC-MS/MS and bioinformatics analyses revealed that ADT-OH treatment inhibited the EMT process in B16F10 and A375 cells by reducing the expression of FAK and the downstream response protein Paxillin. Overexpression of FAK reversed the inhibitory effects of ADT-OH on melanoma cell migration. Moreover, after ADT-OH treatment, melanoma cells showed abnormal expression of the H2S-producing enzymes CSE/CBS and the AKT signaling pathways. In addition, ADT-OH significantly suppressed the proliferation of melanoma cells. Collectively, these results demonstrate that ADT-OH inhibits the EMT process in melanoma cells by suppressing the CSE/CBS and FAK signaling pathways, thereby exerting its antimetastatic activity. ADT-OH may be used as an antimetastatic agent in the future.

Determination of the Median Effective Dose of Dexmedetomidine for the Prevention of Emergence Agitation in Geriatric Patients Undergoing Major Open Surgery With General Anesthesia: A Prospective, Double-Blinded, Dose-Response Trial.

Dexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia. A total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5 µg·kg-1·h-1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by .05 depending on the response of the previous patient, according to the Dixon up-and-down method. An "effective" or "ineffective" response was determined based on the Riker sedation-agitation score (RSAS), we defined "effective" as RSAS<5, and "ineffective" as RSAS≥5. The ED50 of dexmedetomidine in prevention of EA was .30 µg·kg-1·h-1 (95% CI, .27-.33) and the predicted ED95 was .42 µg·kg-1·h-1 (95% CI, .38-.51). The incidence of bradycardia was significantly increased in the group without EA compared to the group with EA (57.1% vs 13.6%, P = .002). The ED50 of dexmedetomidine in prevention of EA was .30 µg·kg-1·h-1 (95% CI, .27-.33) and the predicted ED95 was .42 µg·kg-1·h-1 (95% CI, .38-.51). Bradycardia was the main complication.

Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan.

Clinical trials showed pangenotypic direct-acting antivirals' (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

Harpagide exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress via SERCA following oxygen-glucose deprivation/reoxygenation injury.

Cerebrovascular diseases endanger human health, and the physiological and pathological processes of cerebral ischemia/reperfusion injury (CIRI) are critical for the occurrence of these diseases and as targets for their treatment. Here, we evaluated the effects of harpagide-mediated pharmacological and genetic inhibition of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in vitro in PC12 cells. The molecular mechanism by which harpagide protects PC12 cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury was investigated by evaluating the cell survival rate with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, assessing apoptosis by flow cytometry, determining the intracellular Ca2+ concentration ([Ca2+]i) by laser scanning confocal microscopy (LSCM), and measuring the expression of proteins related to SERCA and endoplasmic reticulum stress (ERS) by Western blotting. The results revealed that harpagide significantly decreased thapsigargin (TG)-induced apoptosis of PC12 cells, downregulated the expression of ERS-related markers, considerably improved the TG-induced expression of SERCA-related proteins and reduced the [Ca2+]i, suggesting that harpagide effectively inhibited ERS directly. Moreover, harpagide did not significantly reduce OGD/R-induced apoptosis but increased the expression of ERS markers in PC12/SERCA- cells, indicating that harpagide targets SERCA to protect against CIRI by suppressing ERS-mediated apoptosis.

High-frequency rectifiers based on type-II Dirac fermions.

The advent of topological semimetals enables the exploitation of symmetry-protected topological phenomena and quantized transport. Here, we present homogeneous rectifiers, converting high-frequency electromagnetic energy into direct current, based on low-energy Dirac fermions of topological semimetal-NiTe2, with state-of-the-art efficiency already in the first implementation. Explicitly, these devices display room-temperature photosensitivity as high as 251 mA W-1 at 0.3 THz in an unbiased mode, with a photocurrent anisotropy ratio of 22, originating from the interplay between the spin-polarized surface and bulk states. Device performances in terms of broadband operation, high dynamic range, as well as their high sensitivity, validate the immense potential and unique advantages associated to the control of nonequilibrium gapless topological states via built-in electric field, electromagnetic polarization and symmetry breaking in topological semimetals. These findings pave the way for the exploitation of topological phase of matter for high-frequency operations in polarization-sensitive sensing, communications and imaging.

Colossal Terahertz Photoresponse at Room Temperature: A Signature of Type-II Dirac Fermiology.

The discovery of Dirac semimetal has stimulated bourgeoning interests for exploring exotic quantum-transport phenomena, holding great promise for manipulating the performance of photoelectric devices that are related to nontrivial band topology. Nevertheless, it still remains elusive on both the device implementation and immediate results, with some enhanced or technically applicable electronic properties signified by the Dirac fermiology. By means of Pt doping, a type-II Dirac semimetal Ir1-xPtxTe2 with protected crystal structure and tunable Fermi level has been achieved in this work. It has been envisioned that the metal-semimetal-metal device exhibits an order of magnitude performance improvement at terahertz frequency when the Fermi level is aligned with the Dirac node (i.e., x ∼ 0.3) and a room-temperature photoresponsivity of 0.52 A·W-1 at 0.12 THz and 0.45 A·W-1 at 0.3 THz, which benefited from the excitation of type-II Dirac fermions. Furthermore, van der Waals integration with Dirac semimetals exhibits superb performance with noise equivalent power less than 24 pW·Hz-0.5, rivaling the state-of-the-art detectors. Our work provides a route to explore the nontrivial topology of Dirac semimetal for addressing targeted applications in imaging and biomedical sensing across a terahertz gap.

Suicide attempts in Chinese Han patients with schizophrenia: cognitive, demographic, and clinical variables

Objective: The purpose of this study was to investigate the lifetime suicide attempt rate, clinical characteristics and cognitive function of Chinese patients with chronic schizophrenia who had attempted suicide. Methods: We collected data from 908 schizophrenia inpatients about suicide attempts through interviews with the patients and their families, as well as through medical records. All patients were assessed with the Positive and Negative Syndrome Scale, the Rating Scale for Extrapyramidal Side Effects, the Abnormal Involuntary Movement Scale, and the Repeated Battery for the Assessment of Neuropsychological Status. Results: Of this sample, 97 (10.68%) had attempted suicide. Patients who had attempted suicide were younger, had longer illness duration, and more severe general psychopathology and depressive symptoms than those who had not. Logistic regression analysis confirmed that suicide attempts were correlated with age, smoking, and depression. No cognitive performance differences were observed between patients who had and had not attempted suicide. Conclusions: In China, patients with chronic schizophrenia may have a higher prevalence of lifetime suicide attempts than the general population. Some demographic and clinical variables were related to suicide attempts in patients with chronic schizophrenia.