Improving the efficiency of CRISPR-Cas12a-based genome editing with site-specific covalent Cas12a-crRNA conjugates.

The CRISPR-Cas12a system shows unique features compared with widely used Cas9, making it an attractive and potentially more precise alternative. However, the adoption of this system has been hindered by its relatively low editing efficiency. Guided by physical chemical principles, we covalently conjugated 5' terminal modified CRISPR RNA (crRNA) to a site-specifically modified Cas12a through biorthogonal chemical reaction. The genome editing efficiency of the resulting conjugated Cas12a complex (cCas12a) was substantially higher than that of the wild-type complex. We also demonstrated that cCas12a could be used for precise gene knockin and multiplex gene editing in a chimeric antigen receptor T cell preparation with efficiency much higher than that of the wild-type system. Overall, our findings indicate that covalently linking Cas nuclease and crRNA is an effective approach to improve the Cas12a-based genome editing system and could potentially provide an insight into engineering other Cas family members with low efficiency as well.

Improved test-retest reliability of R 2 * $$ {\mathrm{R}}_2

PURPOSE: This study aimed to evaluate the potential of 3D EPI for improving the reliability of T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted data and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ decay rate and susceptibility (χ) compared with conventional gradient-echo (GRE)-based acquisition. METHODS: Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ were quantified, and their interscan differences were used to evaluate the test-retest reliability. Interprotocol differences of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ between GRE and EPI were also measured voxel by voxel and in selected regions of interest to test the consistency between the two acquisition methods. RESULTS: The quantifications of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. CONCLUSION: The result suggests that multishot multi-echo 3D EPI can be a useful alternative acquisition method for T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ with reduced scan time, improved test-retest reliability, and similar accuracy compared with commonly used 3D GRE.

Genetic-code-expanded cell-based therapy for treating diabetes in mice.

Inducer-triggered therapeutic protein expression from designer cells is a promising strategy for disease treatment. However, as most inducer systems harness transcriptional machineries, protein expression timeframes are unsuitable for many therapeutic applications. Here, we engineered a genetic code expansion-based therapeutic system, termed noncanonical amino acids (ncAAs)-triggered therapeutic switch (NATS), to achieve fast therapeutic protein expression in response to cognate ncAAs at the translational level. The NATS system showed response within 2 hours of triggering, whereas no signal was detected in a transcription-machinery-based system. Moreover, NATS system is compatible with transcriptional switches for multi-regulatory-layer control. Diabetic mice with microencapsulated cell implants harboring the NATS system could alleviate hyperglycemia within 90 min on oral delivery of ncAA. We also prepared ncAA-containing 'cookies' and achieved long-term glycemic control in diabetic mice implanted with NATS cells. Our proof-of-concept study demonstrates the use of NATS system for the design of next-generation cell-based therapies to achieve fast orally induced protein expression.

Prevalence, characteristics, and risk factors of venous thromboembolism in patients with brain tumor undergoing craniotomy: a meta-analysis.

BACKGROUND: Brain tumor patients undergoing craniotomy are significantly associated with the development of venous thromboembolism (VTE), while the contributing factors remains controversial. Our study aimed to investigate the prevalence and risk factors for VTE in postoperational brain tumor patients. METHODS: We searched the PubMed, Embase, Web of Science, Medline, and Cochrane Library databases from their inception to July 2023. Article selection, data extraction, and study quality assessment were performed independently by two reviewers. Publication bias was assessed using Egger's and Begg's tests. Stata 15.0 software was used for data analysis. RESULTS: A total of 25 studies were considered, with a total of 49,620 brain tumor individuals. The pooled prevalence of VTE during hospitalization in postoperational brain tumor patients was 9% [95% CI: (0.08, 0.10)]. Moreover, our results demonstrated that patients with VTE were older than those without VTE [mean difference [MD] = 8.14, 95% CI: (4.97, 11.30)]. The following variables were significantly associated with VTE: prior history of VTE [OR = 7.81, 95% CI: (3.62, 16.88)], congestive heart failure [OR = 2.33, 95% CI: (1.08-5.05)], diabetes [OR = 1.87, 95% CI: (1.12-3.10)], hypertension [OR = 1.27, 95% CI: (1.07-1.50)], steroid use [OR = 1.63, 95% CI: (1.41, 1.88)], high white blood cells counts [MD = 0.32, 95% CI: (0.01, 0.63)], and high fibrinogen levels [MD = 0.19, 95% CI: (0.08, 0.30)]. CONCLUSION: This meta-analysis identified risk factors for postoperational VTE in patients with brain tumor, which can serve as a theoretical foundation for medical staff to manage and treat VTE. TRIAL REGISTRATION: CRD42023357459.

Using case-based learning supported by role-playing situational teaching method in endocrine physiology education.

Embedding clinically relevant learning experience in basic science subjects is desired for the preclinical phase of undergraduate medical education. The present study aimed to modify case-based learning (CBL) with a role-playing situational teaching method and assess the student feedback and learning effect. One hundred seventy-six sophomore students majoring in clinical medicine from Harbin Medical University were randomly divided into two groups: the control group (n = 90), who received traditional hybrid teaching, and the experimental group (n = 86), who received the role-playing situational teaching. Students in the experimental group were given a 1-wk preclass preparation to dramatize a hyperthyroidism scenario through online autonomous learning of thyroid physiology and performed the patient's consultation process in class, followed by a student presentation about key points of lecture content and a question-driven discussion. A posttest and questionnaire survey were conducted after class. The test scores of the two groups had no statistical differences, whereas the rate of excellence (high scores) of the experimental group was significantly higher than that of the control group. Furthermore, the record of online self-directed learning engagements was significantly improved in the experimental group. In the questionnaire, >70% of the students showed positive attitudes toward the role-playing situational teaching method and were willing to participate in other chapters of the physiology course. Such results show that CBL supported by a role-playing situational teaching method encourages active learning and improves the application of basic knowledge of physiology, which can be incorporated in the preclinical curricula to bridge the gap between theory and practice.NEW & NOTEWORTHY Formal application through structured role-play is often overlooked in physiology education. In traditional case-based learning (CBL), clinical cases are the subject and unfocused discussion often occurs. The present study aimed to modify CBL with a role-playing situational teaching method and assess the student feedback and learning effect. The results show that the new teaching model encourages active learning and improves the application of basic knowledge of physiology.

Effect of motion, cortical orientation and spatial resolution on quantitative imaging of cortical R2* and magnetic susceptibility at 0.3 mm in-plane resolution at 7 T.

MR images of the effective relaxation rate R2* and magnetic susceptibility χ derived from multi-echo T2*-weighted (T2*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R2* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R2* and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T2*w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B0 changes was deployed using volumetric navigators. Such correction improved the T2*w image quality rated by experienced image readers and test-retest reliability of R2* and χ quantification with reduced median inter-scan differences up to 10 s-1 and 5 ppb, respectively. R2* and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s-1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R2* or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R2* and χ along the cortical depth at submillimeter resolution and the need for motion and B0 corrections for their robust quantification in vivo.

Dielectric Matching by the Unique Dynamic Dipoles in Hybrid Organic/Inorganic Superlattices toward Ultrathin Microwave Absorber.

There is an urgent demand of ultrathin high-performance microwave absorbing materials (MAMs) in the electromagnetic protection field. However, minimizing thickness is challenging mainly due to dielectric mismatch at high permittivity from excessive dielectric loss, leading to strong reflection at 2-18 GHz. Here, a hybrid TaS2 /Co(Cp)2 superlattice is fabricated with alternating [TaS2 ] inorganic layers and [Co(Cp)2 ] organic layers. Dynamic Ta─Co dipoles offer a unique interfacial polarization relaxation mechanism involving the inversion and rotation of dynamic Ta─Co dipoles. The prolonged relaxation time of limited dynamic Ta─Co dipoles contributes to enhanced dielectric matching at high permittivity, which is essential for ultrathin high-performance MAMs. Furthermore, the confinement of paramagnetic Co(Cp)2 molecules in the interlayer space of the diamagnetic TaS2 sublattice triggers unexpected ferromagnetism via interfacial magnetic coupling conducive to the improved microwave-absorbing performance at reduced thickness. Therefore, it presents a 1.271-mm thick ultrathin absorber that can attenuate up to 99.99% of electromagnetic wave energy with a broad effective absorption bandwidth of 4.05 GHz, thus pushing the limits of thickness of 2D-based high-performance MAMs. This paper demonstrates a new strategy toward ultrathin MAMs with tunable and decent electromagnetic loss derived from electrical and magnetic coupling at the atomic scale.

Exploring Health Effects under Specific Causes of Mortality Based on 90 Definitions of PM2.5 and Cold Spell Combined Exposure in Shanghai, China.

In this study, a total of 90 definitions were set up based on six air pollution definitions, five cold spell definitions, and three combined exposure scenarios. The relative risks (RRs) on all-cause, circulatory, and respiratory mortality were explored by a model combining a distributed linear lag model with quasi-Poisson regression. The definition in which daily PM2.5 increases more than 75 µg/m3 for at least 2 days and the average temperature falls below the 10th percentile for at least 2 days produced the best model fit performance in all-cause mortality. The high peaks of the health effect were generally observed around the lag days 6-9. The cumulative relative risks (CRRs) were more significant in the simultaneous-exposure scenario and higher in respiratory mortality, where the highest CRR (12.15, 3.69-40.03) was observed in definition P1T5, in which daily PM2.5 increases more than 75 µg/m3, and the average temperature falls below the 2.5th percentile for at least two days. For relative risk due to interaction (RERI), we found positive additive interactions (RERI > 0) between PM2.5 pollution and cold spell, especially in respiratory mortality. Clarifying the definition of combined events can help policymakers to capture health risks and construct more effective risk warning systems.

Positive effects of napping on memory consolidation and resistance against interference.

PURPOSE: This study explored the relationship between naps and memory among habitual nappers in China. METHODS: Medical college students participated and were divided into 30-min, 60-min, and 90-min time-in-bed groups. To evaluate declarative and procedural memory performance, A-B and A-C interfering word pair and interfering finger tapping tasks were employed. RESULTS: Among 60 students, a significant decrease in the correct recall rate in the declarative task after having a nap was found only in the 30-min group (p = 0.005). After learning interference (A-C word pairs), the correct recall rate for the declarative task decreased significantly in all interference tests (ps < 0.001). In the procedural task, the speed of sequence A in the retests increased after having a nap in all three groups (ps < 0.048), with a significant decrease in accuracy only in the 30-min group (p = 0.042). After learning interference (sequence B) in the procedural task, the speed of sequence A increased in the 60-min group after 1 h (p = 0.049), and both the 60-min and 90-min groups showed increased speed after one night (ps < 0.022). No significant improvement in speed was found in the 30-min group (ps > 0.05), and this group showed the lowest accuracy for sequence A (ps < 0.16). CONCLUSION: A habitual nap time-in-bed of 60 or 90 min had better effects on declarative and procedural memory consolidation and better memory resistance against interference in procedural memory.

Resveratrol Protects Rat Ovarian Luteinized Granulosa Cells from H2O2-Induced Dysfunction by Activating Autophagy.

Resveratrol performs a variety of biological activities, including the potential regulation of autophagy. However, it is unclear whether resveratrol protects against luteal dysfunction and whether autophagy involves the regulation of resveratrol. This study aims to investigate whether resveratrol can regulate autophagy to resist H2O2-induced luteinized granulosa cell dysfunction in vitro. Our results showed that resveratrol can enhance cell viability, stimulate the secretion of progesterone and estradiol, and resist cell apoptosis in H2O2-induced luteinized granulosa cell dysfunction. Resveratrol can activate autophagy by stimulating the expression of autophagy-related genes at the transcriptional and translational levels and increasing the formation of autophagosomes and autophagolysosomes. Rapamycin, 3-methyladenine, and bafilomycin A1 regulated the levels of autophagy-related genes in H2O2-induced luteinized granulosa cell dysfunction and further confirmed the protective role of autophagy activated by resveratrol. In conclusion, resveratrol activates autophagy to resist H2O2-induced oxidative dysfunction, which is crucial for stabilizing the secretory function of luteinized granulosa cells and inhibiting apoptosis. This study may contribute to revealing the protective effects of resveratrol on resisting luteal dysfunction from the perspective of regulating autophagy.

Changes in sleep quality among Chinese active service personnel: A cross-temporal meta-analysis, 2003-2019.

Military personnel live in operating environments in which poor sleep is common. In this cross-temporal meta-analysis (CTMA), 100 studies (144 data sets, N = 75,998) were identified to examine changes in sleep quality among Chinese active service personnel from 2003 to 2019. Participants were divided into three groups: the navy, the non-navy, and the unknown service. The Pittsburgh Sleep Quality Index (PSQI) was used as the measure of sleep quality; it contains a global score and seven component scores, with higher scores indicative of poorer sleep. Among all active military personnel, the PSQI global and seven component scores decreased from 2003 to 2019. In examining the results by military type, the PSQI global and seven component scores increased in the navy group. Conversely, both the non-navy and unknown-service groups showed decreased PSQI global scores over time. Similarly, all PSQI component scores decreased over time for both the non-navy and unknown service groups, except for the use of sleeping medication (USM), which increased in the non-navy group. In conclusion, the sleep quality of Chinese active service personnel showed a positive trend. Further research should focus on improving the navy's sleep quality.

The domain of unknown function 4005 (DUF4005) in an Arabidopsis IQD protein functions in microtubule binding.

The dynamic responses of microtubules (MTs) to internal and external signals are modulated by a plethora of microtubule-associated proteins (MAPs). In higher plants, many plant-specific MAPs have emerged during evolution as advantageous to their sessile lifestyle. Some members of the IQ67 domain (IQD) protein family have been shown to be plant-specific MAPs. However, the mechanisms of interaction between IQD proteins and MTs remain elusive. Here we demonstrate that the domain of unknown function 4005 (DUF4005) of the Arabidopsis IQD family protein ABS6/AtIQD16 is a novel MT-binding domain. Cosedimentation assays showed that the DUF4005 domain binds directly to MTs in vitro. GFP-labeled DUF4005 also decorates all types of MT arrays tested in vivo. Furthermore, we showed that a conserved stretch of 15 amino acid residues within the DUF4005 domain, which shares sequence similarity with the C-terminal MT-binding domain of human MAP Kif18A, is required for the binding to MTs. Transgenic lines overexpressing the DUF4005 domain displayed a spectrum of developmental defects, including spiral growth and stunted growth at the organismal level. At the cellular level, DUF4005 overexpression caused defects in epidermal pavement cell and trichome morphogenesis, as well as abnormal anisotropic cell elongation in the hypocotyls of dark-grown seedlings. These data establish that the DUF4005 domain of ABS6/AtIQD16 is a new MT-binding domain, overexpression of which perturbs MT homeostasis in plants. Our findings provide new insights into the MT-binding mechanisms of plant IQD proteins.

Identification of multiple nonphotochemical quenching processes in the extremophilic red alga Cyanidioschyzon merolae.

Nonphotochemical quenching acts as a frontline response to prevent excitation energy from reaching the photochemical reaction center of photosystem II before photodamage occurs. Strong fluorescence quenching after merely one multi-turnover saturating light pulse characterizes a unique feature of nonphotochemical quenching in red algae. Several mechanisms underlying red algal nonphotochemical quenching have been proposed, yet which process(es) dominantly account for the strong fluorescence quenching is still under discussion. Here we assessed multiple nonphotochemical quenching processes in the extremophilic red alga Cyanidioschyzon merolae under light pulse and continuous illumination conditions. To assess the nonphotochemical quenching processes that might display different kinetics, fluorescence emission spectra at 77 K were measured after different periods of light treatments, and external fluorophores were added for normalization of the fluorescence level. The phycobilisome- and photosystem II-related nonphotochemical quenching processes were distinguished by light preferentially absorbed by phycobilisomes and photosystems, respectively. Multiple nonphotochemical quenching processes, including the energetic decoupling of phycobilisomes from photosystem II, the energy spillover from phycobilisomes to photosystem I and from photosystem II to photosystem I, were identified along with the previously identified intrinsic quenching within photosystem II. The ability to use multiple nonphotochemical quenching processes appears to maximize the light harvesting efficiency for photochemistry and to provide the flexibility of the energy redistribution between photosystem II and photosystem I. The effect of the various ionophores on the nonphotochemical quenching level suggests that nonphotochemical quenching is modulated by transmembrane gradients of protons and other cations.

Seasonal Variations in the Characteristics of Microbial Community Structure and Diversity in Atmospheric Particulate Matter from Clean Days and Smoggy Days in Beijing.

Microorganisms are an important part of atmospheric particulate matter and are closely related to human health. In this paper, the variations in the characteristics of the chemical components and bacterial communities in PM10 and PM2.5 grouped according to season, pollution degree, particle size, and winter heating stage were studied. The influence of environmental factors on community structure was also analyzed. The results showed that seasonal variations were significant. NO3- contributed the most to the formation of particulate matter in spring and winter, while SO42- contributed the most in summer and autumn. The community structures in summer and autumn were similar, while the community structure in spring was significantly different. The dominant phyla were similar among seasons, but their proportions were different. The dominant genera were no-rank_c_Cyanobacteria, Acidovorax, Escherichia-Shigella and Sphingomonas in spring; Massilia, Bacillus, Acinetobacter, Rhodococcus, and Brevibacillus in summer and autumn; and Rhodococcus in winter. The atmospheric microorganisms in Beijing mainly came from soil, water, and plants. The few pathogens detected were mainly affected by the microbial source on the sampling day, regardless of pollution level. RDA (redundancy analysis) showed that the bacterial community was positively correlated with the concentration of particulate matter and that the wind speed in spring was positively correlated with NO3- levels, NH4+ levels, temperature, and relative humidity in summer and autumn, but there was no clear consistency among winter samples. This study comprehensively analyzed the variations in the characteristics of the airborne bacterial community in Beijing over one year and provided a reference for understanding the source, mechanism, and assessment of the health effects of different air qualities.

Anshen-Buxin-Liuwei pill, a Mongolian medicinal formula could alleviate cardiomyocyte hypoxia/reoxygenation injury via mitochondrion pathway.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula that is composed of six medicinal materials: the Mongolian medicine Bos taurus domesticus Gmelin, Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt., Eugenia caryophµllata Thunb., Aucklandia lappa Decne., and Liqui dambar formosana Hance. ABLP is considered to have a therapeutic effect on symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and shortness of breath. METHODS: H9c2 cardiomyocytes were used to construct a hypoxia/reoxygenation (HR) injury model. CCK-8 assay and Annexin V-FITC cell apoptosis assays were used for cell viability and cell apoptosis determination. The LDH, SOD, MDA, CAT, CK, GSH-Px, Na+-K+-ATPase, and Ca2+-ATPase activities in cells were determined to assess the protective effects of ABLP. The mRNA levels of Sirtuin3 (Sirt3) and Cytochrome C (Cytc) in H9c2 cells were determined by quantitative real-time PCR. RESULTS: The results indicate that HR-treated cells began to shrink from the spindle in an irregular shape with some floated in the medium. By increasing the therapeutic dose of ABLP (5, 25, and 50 µg/mL), the cells gradually reconverted in a concentration-dependent manner. The release of CK in HR-treated cells was significantly increased, indicating that ABLP exerts a protective effect in H9c2 cells against HR injury and can improve mitochondrial energy metabolism and mitochondrial function integrity. The present study scrutinized the cardioprotective effects of ABLP against HR-induced H9c2 cell injury through antioxidant and mitochondrial pathways. CONCLUSIONS: ABLP could be a promising therapeutic drug for the treatment of myocardial ischemic cardiovascular disease. The results will provide reasonable information for the clinical use of ABLP.

A pooled analysis of adding olanzapine to guideline-recommended antiemetic therapy for breast cancer patients treated with an anthracycline and cyclophosphamide in prospective and retrospective studies.

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

Exploring a more reasonable temperature exposure calculation method based on individual exposure survey and city-scale heat exposure impact assessment.

The inability to quantify the difference between ambient temperature (AT) and personal exposure temperature (PET) is a common limitation in environmental health research. The actual exposure variability is underestimated when we used measurements from fixed monitoring stations to estimate PET. The study aims to explore a more reasonable temperature exposure calculation method to relate PET to AT and links heat exposure to adverse health events. We measured hourly PET of 129 participants from July 8th to July 13th, 2021 in Xinyi City, China. The linear mixed-effects model was used to build the relationship between hourly PET and AT in rural and town. Several calculation methods that can capture the intensity, frequency and duration of daily exposure were used to calculate the daily PET and AT and establish the relationship between the two factors. A generalized linear model was used to establish the relationship between city-scale AT indicators and health endpoints from January 1st, 2013 to December 31st, 2015 in Shanghai, China. The result showed that the hourly PET was significantly related to AT, wind speed, air pressure, precipitation, outside time, and air-conditioning use. Among several daily temperature indicators, we found that ATDHAT (Degree Hours Above Threshold (27.4 °C)) was tight with the PETDHAT in different regions (R2 > 0.99). DHAT strengthened the relationship between daily AT and health endpoint in the urban-scale heat-related health impact study, especially in respiratory diseases. The method proposed in this study can improve the accuracy of future epidemiological studies on the effects of heat exposure.

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.

Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.

Nursing allocation in isolation wards of COVID-19 designated hospitals: a nationwide study in China.

BACKGROUND: Appropriate allocation of nursing staff is key to ensuring efficient nursing in hospitals, and is significantly correlated with patient safety, nursing quality, and nurse job satisfaction. However, there are few studies on nursing workforce allocation in the isolation wards of COVID-19 designated hospitals globally. This study aims to better understand the nursing workforce allocation in the isolation wards of COVID-19 designated hospitals in China, and provide a theoretical basis for efficiently deploying first-line nurses in China and across the world in the future. METHODS: An online survey was conducted among the head nurses (n = 229) and nurses (n = 1378) in the isolation wards of 117 hospitals (selected by stratified sampling), using a self-reported human resource allocation questionnaire. RESULTS: The average bed-to-nurse ratios of different isolation wards were different (Z = 36.742, P = 0.000). The bed-to-nurse ratios of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, were 1:1.88, 1:0.56, and 1:0.45, respectively. The nurse work hours per shift in different isolation wards were also different (Z = 8.468, P = 0.014), with the specific values of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, being 5, 6, and 6 h, respectively. A correlation analysis showed that the average work hours per shift was proportional to the overtime work of nurses (rs = 0.146), the proportion of nurse practitioners was proportional to the overall utilization rate of nursing human resources in the wards (rs = 0.136), and the proportion of nurses with college degrees was proportional to teamwork (rs = 0.142). The proportion of nurses above grade 10 was inversely proportional to teamwork and psychological problems (rs = 0.135, rs = 0.203). The results of multiple stepwise regression analyses showed that the work hours of nurses per shift was the main factor affecting nurse satisfaction and that the proportion of nurses and the work hours of nurses per shift were both independent factors affecting the length of stay (LOS) of patients. CONCLUSION: Hospitals in China have made good nursing workforce allocations during the COVID-19 pandemic, but there are certain shortcomings. Therefore, scientific and efficient nursing workforce allocation practice plans should be established to improve the ability of hospitals to deal with public health emergencies and are urgent problems that need to be addressed soon.

Genetic polymorphisms and haplotypes of ERCC1 and ERCC2 associated with quality of life, depression, and anxiety status among patients with lung cancer.

BACKGROUND: Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC. METHODS: QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis. RESULTS: ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009). CONCLUSION: After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients.