Electrochemical quinuclidine-mediated Minisci-type acylation of N-heterocycles with aldehydes.

The electro-generation of acyl radicals from both aromatic and aliphatic aldehydes remains an unmet challenge. We provide a solution to this challenge by merging electro-oxidation and a quinuclidine-mediated hydrogen atom transfer strategy. The generation of acyl radicals at decreased applied potentials compared to that of formyl oxidation exhibits excellent functional group compatibility.

Quality of Life and Emotional Problems of COVID-19 Patients after Discharge: A One-Month Longitudinal Study.

AIM: The first coronavirus disease 2019 (COVID-19) outbreak in Taiwan occurred in May 2021 and many individuals were infected. All COVID-19 patients were quarantined in designated facilities until they fully recovered to prevent the spread of the disease. Prolonged quarantine could adversely affect these patients. In this study, we focused on investigating changes in the quality of life and mental health of individuals discharged from hospital after recovering from COVID-19. METHODS: This study employed a longitudinal design and surveyed individuals discharged from a teaching hospital in northern Taiwan in 2021 within one week of their discharge and again after one month. An online questionnaire comprising the participants' background, respiratory function (COPD Assessment Test), quality of life (WHOQoL-BREF), and emotional problems (DASS-21) was administered to the participants. RESULTS: A total of 56 participants actively took part in both surveys. We observed that participants with abnormal respiratory function had a lower physical and psychological quality of life, especially those with severe symptoms requiring endotracheal intubation during the treatment period of COVID-19. Additionally, approximately 30% of participants experienced anxiety problems throughout this study period. Finally, patients with COVID-19 symptoms exhibited a lower quality of life and higher levels of severe emotional problems. CONCLUSIONS: According to our findings, it is necessary to monitor and provide appropriate interventions for individuals who have recovered from COVID-19, especially those who experienced severe symptoms that required endotracheal intubation during COVID-19 treatment. These interventions, such as symptom management and psychological support, can help improve their quality of life and reduce emotional problems. Therefore, after the participants are discharged, hospitals should regularly track the patients' status and provide appropriate support or referrals to help these individuals. Otherwise, future research could include more participants and follow up with them for longer to investigate the longitudinal impact of COVID-19.

Paired Electrolysis Enabled Trifluoromethylheteroaromatization of Alkenes and Alkyne with Trifluoromethyl Thianthrenium Triflate (TT-CF3+OTf-) as a Bifunctional Reagent.

We report a strategic exploitation of trifluoromethyl thianthrenium triflate (TT-CF3+OTf-) as both electromediator and CF3 radical precursors for paired electrolysis. Enabled by this strategy, the three-component trifluoromethylheteroaromatization of alkenes and alkynes was realized. The superiority of TT-CF3+OTf- to other electrophilic CF3 reagents is attributed to the cathodic generation of thianthrene (TT) as a mediator, which shifts the heterogeneous oxidation of interest to a homogeneous one.

Hemoglobin and Its Z Score Reference Intervals in Febrile Children: A Cohort Study of 98,572 Febrile Children.

OBJECTIVES: Febrile disease and age of children were associated with a variation in hemoglobin (Hb) level. Both CRP and Hb serve as laboratory markers that offer valuable insights into a patient's health, particularly in relation to inflammation and specific medical conditions. Although a direct correlation between CRP and Hb levels is not established, the relationship between these markers has garnered academic attention and investigation. This study aimed to determine updated reference ranges for Hb levels for age and investigated its correlation with CRP in febrile children under the age of 18. METHODS: This is a cohort study of in Chang Gung Memorial Hospitals conducted from January 2010 to December 2019. Blood samples were collected from 98,572 febrile children who were or had been admitted in the pediatric emergency department. The parameters of individuals were presented as the mean ± standard deviation or 2.5th and 97.5th percentiles. We also determined the variation of Hb and Z score of Hb between CRP levels in febrile children. RESULT: We observed that the Hb levels were the highest immediately after birth and subsequently underwent a rapid decline, reaching their lowest point at around 1-2 months of age, and followed by a steady increment in Hb levels throughout childhood and adolescence. In addition, there was a significant and wide variation in Hb levels during the infant period. It revealed a significant association between higher CRP levels and lower Hb levels or a more negative Z score of Hb across all age subgroups. Moreover, in patients with bacteremia, CRP levels were higher, Hb concentrations were lower, and Z scores of Hb were also lower compared to the non-bacteremia group. Furthermore, the bacteremia group exhibited a more substantial negative correlation between CRP levels and a Z score of Hb (r = -0.41, p < 0.001) compared to the non-bacteremia group (r = -0.115, p < 0.049). CONCLUSION: The study findings revealed that the Hb references varied depending on the age of the children and their CRP levels. In addition, we established new reference values for Hb and its Z scores and explore their relationship with CRP. It provides valuable insights into the Hb status and its potential association with inflammation in febrile pediatric patients.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

Comparative Effectiveness of Two Models of Point-of-Care Ultrasound for Detection of Post-Void Residual Urine during Acute Ischemic Stroke: Preliminary Findings of Real-World Clinical Application.

We conducted a comparative study of two models of point-of-care ultrasound devices for measuring post-void residual urine (PVRU). We prospectively enrolled 55 stroke inpatients who underwent both real-time B-mode ultrasound (Device A) and automated three-dimensional (3D) scanning ultrasound (Device B), with a total of 108 measurements. The median PVRU volume of Device B was 40 mL larger than that of Device A. The PVRU difference between the devices was positively and linearly correlated with PVRU. The correlation of PVRU volume between the devices was strong, but the agreement level was only moderate. Measurement deviations were observed in 43 (40%) and 11 (10%) measurements with Device B and Device A, respectively. The PVRU volume was low in spherical bladder shapes but sequentially increased in triangular, undefined, ellipsoid, and cuboid bladder shapes. Further comparison of 60 sets of PVRU without measurement deviations revealed higher agreements between the devices at correction coefficients of 0.52, 0.66, and 0.81 for PVRU volumes of <100, 100-200, and >200 mL, respectively. The automated 3D scanning ultrasound is more convenient for learning and scanning, but it exhibits larger measurement deviations. Real-time B-mode ultrasound accurately visualizes the urinary bladder but tends to underestimate the urinary bladder when the PVRU volume is large. Hence, real-time B-mode ultrasound with automated PVRU-based adjustment of calculation formulas may be a better solution for estimating bladder volume.

Reduced graphene oxide-wrapped La0·8Sr0·2MnO3 microspheres sensing electrode for highly sensitive nitrite detection.

An electrochemical nitrite sensor based on perovskite oxides La0·8Sr0·2MnO3 (LSM) microspheres-decorated reduced graphene oxide (rGO) composite was presented to take the merit of the excellent electrocatalytic activity of the LSM and the large surface area of rGO. The content of rGO has been finely adjusted and the electrochemical sensor employing 15 wt% rGO has shown an ultralow nitrite detection limit of 0.016 µM and a high sensitivity of 0.041 µA µM-1 cm-2 and 0.039 µA µM-1 cm-2 in the range of 2-100 and 100-5000 µM, respectively. In addition, the proposed electrode shows good selectivity, reproducibility and stability, suitable for detection of nitrite at various pH values. The sensor was used to determine the nitrite level in environmental water samples with acceptable relative error, demonstrating its feasibility for practical environmental monitoring.

A gating mechanism of the BsYetJ calcium channel revealed in an endoplasmic reticulum lipid environment.

The transmembrane BAX inhibitor-1-containing motif 6 (TMBIM6) is suggested to modulate apoptosis by regulating calcium homeostasis in the endoplasmic reticulum (ER). However, the precise molecular mechanism underlying this calcium regulation remains poorly understood. To shed light on this issue, we investigated all negatively charged residues in BsYetJ, a bacterial homolog of TMBIM6, using mutagenesis and fluorescence-based functional assays. We reconstituted BsYetJ in membrane vesicles with a lipid composition similar to that of the ER. Our results show that the charged residues E49 and R205 work together as a major gate, regulating calcium conductance in these ER-like lipid vesicles. However, these residues become largely inactive when reconstituted in other lipid environments. In addition, we found that D195 acts as a minor filter compared to the E49-R205 dyad. Our study uncovers a previously unknown function of BsYetJ/TMBIM6 in the calcium-dependent inactivation of BsYetJ, providing a framework for the development of a lipid-dependent mechanistic model of BsYetJ that will facilitate our understanding of calcium-dependent apoptosis.

Methods to improve the accuracy of next-generation sequencing.

Next-generation sequencing (NGS) is present in all fields of life science, which has greatly promoted the development of basic research while being gradually applied in clinical diagnosis. However, the cost and throughput advantages of next-generation sequencing are offset by large tradeoffs with respect to read length and accuracy. Specifically, its high error rate makes it extremely difficult to detect SNPs or low-abundance mutations, limiting its clinical applications, such as pharmacogenomics studies primarily based on SNP and early clinical diagnosis primarily based on low abundance mutations. Currently, Sanger sequencing is still considered to be the gold standard due to its high accuracy, so the results of next-generation sequencing require verification by Sanger sequencing in clinical practice. In order to maintain high quality next-generation sequencing data, a variety of improvements at the levels of template preparation, sequencing strategy and data processing have been developed. This study summarized the general procedures of next-generation sequencing platforms, highlighting the improvements involved in eliminating errors at each step. Furthermore, the challenges and future development of next-generation sequencing in clinical application was discussed.

An Algorithm-optimized Scheme for In situ Synthesis of DNA Microarrays.

BACKGROUND: The cost of synthetic DNA has limited applications in frontier science and technology fields such as synthetic biology, DNA storage, and DNA chips. OBJECTIVE: The objective of this study is to find an algorithm-optimized scheme for the in situ synthesis of DNA microarrays, which can reduce the cost of DNA synthesis. METHODS: Here, based on the characteristics of in situ chemical synthesis of DNA microarrays, an optimization algorithm was proposed. Through data grading, the sequences with the same base at as many different features as possible were synthesized in parallel to reduce synthetic cycles. RESULTS AND DISCUSSION: The simulation results of 10 and 100 randomly selected sequences showed that when level=2, the reduction ratio in the number of synthetic cycles was the largest, 40% and 32.5%, respectively. Subsequently, the algorithm-optimized scheme was applied to the electrochemical synthesis of 12,000 sequences required for DNA storage. The results showed that compared to the 508 cycles required by the conventional synthesis scheme, the algorithmoptimized scheme only required 342 cycles, which reduced by 32.7%. In addition, the reduced 166 cycles reduced the total synthesis time by approximately 11 hours. CONCLUSIONS: The algorithm-optimized synthesis scheme can not only reduce the synthesis time of DNA microarrays and improve synthesis efficiency, but more importantly, it can also reduce the cost of DNA synthesis by nearly 1/3. In addition, it is compatible with various in situ synthesis methods of DNA microarrays, including soft-lithography, photolithography, a photoresist layer, electrochemistry and photoelectrochemistry. Therefore, it has very important application value.

Solvent-Responsive Magnetic Beads for Accurate Detection of SARS-CoV-2.

Although numerous approaches were proposed for the nucleic acid (NA)-based SARS-CoV-2 detection, the nonideal NA desorption efficiency of conventional magnetic beads (MBs) limits their widespread application. In this study, we developed solvent-responsive MBs (called responsive MBs), which, in the presence of buffers, modulated the absorption and desorption capacities of NA by flipping the surface -COO-. Relative to other commercial MBs, responsive MBs exhibited similar absorption profiles and markedly enhanced desorption profiles. When applied for NA detection of complex samples, responsive MBs exhibited better performance of RNA detection than DNA, with obvious advantages in sensitivity. Specifically, the RNA and DNA desorption rates of commercial MBs were ∼85 and 82.5%, while those of responsive MBs were nearly 94 and 93.5%, respectively. Furthermore, responsive MBs exhibited remarkable extraction ability in a wide range of tissues and better performance of RNA extraction than DNA. When applied for SARS-CoV-2 detection, the responsive MBs along with the simulated digital RT-LAMP (a previously established apparatus) further improved detection efficiency, yielding a precise quantitative detection as low as 25 copies and an ultimate sensibility detection of 5 copies/mL. It was also successfully employed in numerous NA-based technologies such as polymerase chain reaction (PCR), sequencing, and so on.

6His-tatritin promotes antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp (Ctenopharyngodon idella).

Antimicrobial peptides are small, cationic, and amphiphilic peptides found in most organisms, and many of these peptides have broad antimicrobial activity against Gram-negative, -positive bacteria and fungi. In the present study, a derivative of antimicrobial peptide Tatritin, 6His-Tatritin, was designed and expressed by Pichia pastoris using a constitutive vector pGAPZαA with the promoter of pGAP. The 6His-Tatritin had a broad-spectrum antibacterial activity based on the Oxford cup method and the micro broth dilution test. In addition, to explore the role of 6His-Tatritin in vivo, grass carps (Ctenopharyngodon idellus) were infected with Aeromonas hydrophila after they were fed with 6His-Tatritin as feed additives for 28 days. The results revealed that 6His-Tatritin could significantly up-regulate the expression levels of Hepcidin, Leap-2b, Nrf-2, CuZn-SOD and LZM (P < 0.05). In addition, 6His-Tatritin could significantly reduce the mortality (P < 0.05) and the intestinal injury of grass carps infected with bacteria. The 16S sequencing analysis showed that the structure of microbial community in intestine of fish was more diversified compared with control after treatment with 6His-Tatritin. In summary, the peptide of 6His-Tatritin could promote antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp. This study provides an effective method and approach for the application of antimicrobial peptide Tatritin in aquaculture, and also provides insights into the function of antimicrobial peptides in immunity against pathogens in fish.

Analysis of mutational genotyping using correctable decoding sequencing with superior specificity.

The ability to accurately identify SNPs or low-abundance mutations is important for early clinical diagnosis of diseases, but the existing high-throughput sequencing platforms are limited in terms of their accuracy. Here, we propose a correctable decoding sequencing strategy that may be used for high-throughput sequencing platforms. This strategy is based on adding a mixture of two types of mononucleotides, natural nucleotide and cyclic reversible termination (CRT), for cyclic sequencing. Using the synthetic characteristic of CRTs, about 75% of the calls are unambiguous for a single sequencing run, and the remaining ambiguous sequence can be accurately deduced by two parallel sequencing runs. We demonstrate the feasibility of this strategy, and its cycle efficiency can reach approximately 99.3%. This strategy is proved to be effective for correcting errors and identifying whether the sequencing information is correct or not. And its conservative theoretical error rate was determined to be 0.0009%, which is lower than that of Sanger sequencing. In addition, we establish that the information of only a single sequencing run can be used to detect samples with known mutation sites. We apply this strategy to accurately identify a mutation site in mitochondrial DNA from human cells.

Nitrosoarenes Implement Cascade Cyclization of 1-Allenyl-2-alkynylbenzenes through Diradical Mechanism.

This work reports cascade cyclization between 1-allenyl-2-alkynylbenzenes and nitrosoarenes. When these two components reacted alone under N2, N,O-functionalized indane-fused isoxazolidines 3 were obtained selectively. DFT calculations verify that this reaction sequence involves unprecedented nitrone/alkyne cycloadditions, followed by diradical rearrangement.

Relationship between nurses' resilience and depression, anxiety and stress during the 2021 COVID-19 outbreak in Taiwan.

AIM: The COVID-19 outbreak in Taiwan had a significant impact on medical services. These changes posed a threat to nurses' mental health. Resilience may protect nurses from the psychological impact of COVID-19. This study aimed to understand nurses' resilience and its relationship with nurses' characteristics (life and work situations) and mental health (depression, anxiety and stress) during the outbreak. DESIGN: A cross-sectional study. METHODS: This study surveyed the nurses at a hospital from 9 August 2021, to 20 August 2021. The content of the questionnaire included nurses' characteristics, resilience and mental health. RESULTS: There was an association between higher resilience and lower mental health problems. We also found that some nurses' characteristics were positively correlated with mental health problems. CONCLUSION: Some nurses' life and work situations predicted high levels of mental health problems during the pandemic. Additionally, higher levels of resilience were associated with lower levels of mental health problems.

Survival of compromised adult sensory neurons involves macrovesicular formation.

Adult neurons are recognized as post-mitotically arrested cells with limited regenerative potential. Given these restraints, it is perplexing how neurons sustain routine physiological and occasional reparative stress without compromising their density and integrity. We observed that specific insults or physiological alterations drive adult sensory neurons to attempt cell cycle entry. In this context, we demonstrate that at least a small population of sensory neurons modify their cytoskeleton as a survival mechanism in settings of growth arrest and associated stress. Most notably, among their apparent survival modifications is included a unique, and uncharacterized form of macrovesicle shedding and a subsequent neuron size adjustment. Using time-lapse imaging, we demonstrate macrovesicle shedding in some neurons subjected to growth restraint, but not associated with apoptosis. In axotomized neurons in vivo, cell cycle entry was rare to absent and macrovesicles were not observed, but we nonetheless identified changes in mRNA associated with autophagy. In vivo, neighbouring macrophages may have a role in modifying the neuron cytoskeleton after axotomy. Overall, the findings identify previously unrecognized structural adaptations in adult sensory neurons that may provide resilience to diverse insults.

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH4I.

The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including ß-keto ester, ß-keto amide, ß-keto nitrile, ß-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically, the in situ generated α-iodoketone was proposed to be the key active species.

Comparative Effectiveness of Focused Extracorporeal versus Radial Extracorporeal Shockwave Therapy for Knee Osteoarthritis-Randomized Controlled Study.

Both focused extracorporeal shockwave (f-ESWT) and radial extracorporeal shockwave therapy (r-ESWT) can alleviate symptoms in patients with knee osteoarthritis, but no trials have directly compared f-ESWT with r-ESWT for knee osteoarthritis. This study aimed to compare the effectiveness of f-ESWT and r-ESWT on knee osteoarthritis. Forty-two patients with bilateral knee osteoarthritis were randomly assigned to receive three sessions of either f-ESWT or r-ESWT at 1-week intervals. The patients were evaluated at baseline and at 4 and 8 weeks after the final treatment. The primary outcome was the change in pain intensity, as measured on the visual analog scale (VAS). Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion of the knee joint, and the 6-minute walk test. At the end of 4 weeks, the VAS score was substantially reduced in both groups (f-ESWT, -4.5 ± 2.5 points; r-ESWT, -2.6 ± 2.0 points), with a greater reduction in the f-ESWT group. Both groups showed significant improvement in secondary outcomes; however, the f-ESWT group yielded greater improvement in the VAS score, WOMAC score, and 6-minute walk test. Our results showed that f-ESWT was more effective than r-ESWT in improving pain and physical function in patients with knee osteoarthritis.

Predictive Value of Serum Cholic Acid and Lithocholic Acid for the Diagnosis in an Intrahepatic Cholestasis of Pregnancy Population with High Levels of Total Bile Acids and the Correlation with Placental Hypoxia-Inducible Factor-1α.

Objective: This study aimed to investigate the ability of serum cholic acid (CA) and lithocholic acid (LCA) in the diagnosis and perinatal prognosis assessment of intrahepatic cholestasis of pregnancy (ICP), and the relationship between both indicators and hypoxia-inducible factor-1α (HIF-1α). Methods: Between March 2020 and March 2021, pregnant women with high levels of total bile acid (TBA) in the late pregnancy with TBA ≥10 µmol/L and TBA <10 µmol/L (control group) were included for the retrospective study. Those with TBA ≥10 µmol/L were divided into the ICP group and the asymptomatic hypercholanaemia of pregnancy (AHP) group based on ICP symptoms. The comparison of the bile acid profiles, the receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were conducted successively. Results: Nine types of bile acids were significantly higher in ICP and AHP than in the control group, while CA and LCA serum levels in the AHP group were significantly lower than those in the ICP group (P < 0.05). The ROC curve analysis showed that LCA, CA, and LCA+CA were all diagnostic indicators for ICP, and LCA+CA displayed the greatest diagnostic value (area under the curve (AUC), 0.923). Subgroup analysis using the LCA+CA cut-off point (3.28 µmol/L) as the subgroup indicator proved that the incidence of adverse perinatal outcomes and the placental HIF-1α positivity were significantly higher in the high LCA+CA group than in the low LCA+CA group (P < 0.05). Pearson correlation analysis revealed significant positive correlations of HIF-1α expression levels to LCA, CA and LCA+CA (r = 0.473, 0.537, 0.619, respectively. P < 0.05 in all). Conclusion: This study confirmed that CA and LCA have a predictive diagnostic value for ICP in pregnant women, and the combined evaluation is associated with adverse perinatal outcomes, and LCA+CA positively correlates to placental HIF-1α expression levels.