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Abstract: SARS-CoV-2 is a disease that endangers both human life and the economy. There was an 11- month period of relative evolutionary standstill following the appearance of SARS-CoV-2 in late 2019. However, the emergence of clusters of mutations known as' variants of concern 'with variable viral properties such as transmissibility and antigenicity defined the evolution of SARS-CoV-2. Several efforts have been made in recent months to understand the atomic level properties of SARS-CoV-2. A review of the literature on SARS-CoV-2 mutations is offered in this paper. The critical activities performed by different domains of the SARS-CoV-2 genome throughout the virus's entry into the host and overall viral life cycle are discussed in detail. These structural traits may potentially pave the way for the development of a vaccine and medication to combat the SARS-CoV-2 sickness.

Aims: The objective of the study was to investigate: (1) the Ns genome donor and elucidate the origins of the Xm genome of Leymus; (2) evaluate the phylogenetic relationships among these species. Methodology: The CTAB (cetyltrimethylammonium bromide) procedure was used to extract total genomic DNA from fresh leaf tissue. A total of 150 pairs of SSR primers were tested to screen those produced polymorphic DNA bands to continue further analysis with Elymus species and 13 diploid perennial species as templates. The GS was used to construct a dendrogram via the unweighted pair group method with arithmetic average (UPGMA) and the SHAN (sequential, hierarchical, agglomerative, and nested clustering) routine in the NTSYS-pc program. Results: The primers WMC475, WMC11 and QWM213 showed more expansion efficiency in the research. There were significant diversity and polymorphism between Leymus and related diploid Triticeae species based on SSR makers. The largest GS coefficient values between Pse. stipifolia and Elymus hystrix indicates that the genetic distance is the closest and has a closer genetic relationship. In clade I, the Leymus species formed a very wellsupported into a small distinct group (Ia) first. Specifically, L. racemosus, L. salinus, L. secalinus and L. triticoides were clustered closely. Conclusion: Psathyrostachys juncea, Psa. huanshanica and Psa. fragilis (Ns genome) clustered together into clade I with Leymus species, which further illustrates Leymus that contains Ns genome is more closely related to Psathyrostachys. St genome and J genome did not participate in the origin of Leymus, and the genetic relationship and genetic distance of Leymus species are related to geographical distribution and environment.

Background: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. Methods: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (K Ca 2.3 and K Ca 3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. Results: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial K Ca 2.3 or K Ca 3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of K Ca 2.3/K Ca 3.1 with elevated cytosolic Ca 2+ . Further, chronic S1P stimulation enhanced expression of K Ca 2.3 and K Ca 3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca 2+ signaling or downstream Ca 2+ -activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of K Ca 2.3 and K Ca 3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of K Ca 2.3 and K Ca 3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. Conclusions: This study provides evidence for the mechanistic role of K Ca 2.3/K Ca 3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.

Evaluation is the foundation of automated program repair (APR), as it provides empirical evidence on strengths and weaknesses of APR techniques. However, the reliability of such evaluation is often threatened by various introduced biases. Consequently, bias exploration, which uncovers biases in the APR evaluation, has become a pivotal activity and performed since the early years when pioneer APR techniques were proposed. Unfortunately, there is still no methodology to support a systematic comprehension and discovery of evaluation biases in APR, which impedes the mitigation of such biases and threatens the evaluation of APR techniques. In this work, we propose to systematically understand existing evaluation biases by rigorously conducting the first systematic literature review on existing known biases and systematically uncover new biases by building a taxonomy that categorizes evaluation biases. As a result, we identify 17 investigated biases and uncover a new bias in the usage of patch validation strategies. To validate this new bias, we devise and implement an executable framework APRConfig , based on which we evaluate three typical patch validation strategies with four representative heuristic-based and constraint-based APR techniques on three bug datasets. Overall, this article distills 13 findings for bias understanding, discovery, and validation. The systematic exploration we performed and the open source executable framework we proposed in this article provide new insights as well as an infrastructure for future exploration and mitigation of biases in APR evaluation.

BACKGROUND: It is estimated that 1.95% and 5.55% of adults in China suffer from subclinical thyroid diseases, which is difficult to diagnose and treat. OBJECTIVE: This study aimed to explore the development and prognosis of subclinical thyroid diseases to provide a reference from our single center experience. METHODS: A total of 240 cases from April 2019 to August 2021 in the laboratory information system database of Huanghua Development Boai Hospital were retrospectively analyzed. Binary logistic regression was conducted to analyze odds ratio (OR) of subclinical thyroid disease types returning to a normal state. RESULTS: Among the patients hypothyroidism Ia and hyperthyroidism Ia were the most common type with conversion to the normal state (P< 0.001). TSH level of patients with conversion to a normal state was significantly lower than that of those who developed to abnormal disease (P= 0.015). The OR values of hyperthyroidism Ia and hypothyroidism Ia that returned to a normal state compared with hyperthyroidism Ib were 2.659 (1.159 ∼ 6.096, P= 0.021) and 3.138 (1.1.278 ∼ 7.709, P= 0.013), respectively. The OR value of hypothyroidism Ib that returned to normal compared with hyperthyroidism Ib was 0.629 (0.131 ∼ 3.010, P= 0.561). Thyroid hormone levels, age, and gender at first diagnosis were not impact factor for prognosis of subclincal thyroid disease (P> 0.05). CONCLUSION: Cases with grade hypothyroidism Ia and hyperthyroidism Ia are more likely to revert to normal state than other subclinical thyroid diseases. TSH reference range should be explored for diagnosis and treatment.

Growth hormone (GH), which is commonly considered to be a promoter of growth and development, has direct and indirect effects on adult gonads that influence reproduction and sexual function of humans and nonhumans. GH receptors are expressed in adult gonads in some species including humans. For males, GH can improve the sensitivity of gonadotropins, contribute to testicular steroidogenesis, influence spermatogenesis possibly, and regulate erectile function. For females, GH can modulate ovarian steroidogenesis and ovarian angiogenesis, promote the development of ovarian cells, enhance the metabolism and proliferation of endometrial cells, and ameliorate female sexual function. Insulin-like growth factor-1 (IGF-1) is the main mediator of GH. In vivo, a number of the physiological effects of GH are mediated by GH-induced hepatic IGF-1 and local IGF-1. In this review, we highlight the roles of GH and IGF-1 in adult human gonads, clarify potential mechanisms, and explore the efficacy and the risk of GH supplementation in associated deficiency and assisted reproductive technologies. Besides, the effects of excess GH on adult human gonads are discussed as well.

Introduction: Adenoidectomy is a common procedure in children who have adenoid hypertrophy (AH), but anesthesia risks should be considered. We proposed a novel classification system for adenoids based on their appearance. Additionally, we explored whether the novel classification of adenoids correlates with the response to therapy and thus might be helpful for further treatment recommendations. Methods: We used fiberoptic nasal endoscopy to determine the degree and appearance of AH. Obstructive Sleep Apnea Questionnaire (OSA-18) was used to assess the quality of life of children with AH. The adenoids were divided into three types: edematous type, common type, and fibrous type. In adenoid tissues, the eosinophils were counted. Immunohistochemistry and Western blot were done to determine the expression of CysLTR1, CysLTR2, CGR-α, and CGR-β in different types of adenoids. Results: 70.67% (106/150) of AH patients presented with allergic rhinitis (AR), and of them, 68% (72/106) of adenoids were the edematous type. The expressions of CGR-α, CGR-β, and eosinophil count were higher in the edematous compared with the common and fibrous types. The expression of the leukotriene receptor was similar in all types. Upon montelukast combined with nasal glucocorticoid therapy, improvement of OSA-18 scores and AH grade was significantly compared to montelukast monotherapy for edematous type. There was not any statistically significant difference between the scores upon montelukast combined with nasal glucocorticoid and montelukast monotherapy for common and fibrous type. We observed a positive correlation between eosinophil count in the blood and in the adenoid tissue. Conclusion: AR was the risk factor for the development of edematous AH. All subtypes of AH responded to montelukast, while there was an additional effect of nasal glucocorticoid in the edematous type. A combination therapy of nasal glucocorticoid with leukotriene receptor antagonist can be recommended for AH patients with AR, patients with edematous adenoids, and/or patients with increased eosinophils in blood routine.

Mid-air text entry on virtual keyboards suffers from the lack of tactile feedback, which brings challenges to both tap detection and input prediction. In this paper, we explored the feasibility of single-finger typing on virtual QWERTY keyboards in mid-air. We first conducted a study to examine users' 3D typing behavior on different sizes of virtual keyboards. Results showed that the participants perceived the vertical projection of the lowest point on the keyboard during a tap as the target location and inferring taps based on the intersection between the finger and the keyboard was not applicable. Aiming at this challenge, we derived a novel input prediction algorithm that took the uncertainty in tap detection into a calculation as probability, and performed probabilistic decoding that could tolerate false detection. We analyzed the performance of the algorithm through a full-factorial simulation. Results showed that the SVM-based probabilistic touch detection together with a 2D elastic probabilistic decoding algorithm (elasticity = 2) could achieve the optimal top-5 accuracy of 94.2%. In the evaluation user study, the participants reached a single-finger typing speed of 26.1 WPM with 3.2% uncorrected word-level error rate, which was significantly better than both tap-based and gesture-based baseline techniques. Also, the proposed technique received the highest preference score from the users, proving its usability in real text entry tasks.

AimTo describe the clinical characteristics in a cohort of patients with the pachychoroid phenotype and to evaluate the association of ocular and systemic factors with type of complications observed.MethodsWe report baseline findings from a prospective observational study which recruited subjects with subfoveal choroidal thickness (SFCT) of ≥300 µm on spectral-domain optical coherence tomography (OCT). Multimodal imaging was used to classify eyes as uncomplicated pachychoroid (UP) or pachychoroid disease with pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC) or pachychoroid neovasculopathy (PNV) subtypes.ResultsAmong 181 eyes of 109 participants (mean age 60.6 years, 33 (30.3%) female, 95 (7.2%) Chinese), 38 eyes (21.0%) had UP. Of 143 eyes (79.0%) with pachychoroid disease, 82 (45.3%), 41 (22.7%) and 20 (11.0%) had PPE, CSC and PNV, respectively. Addition of autofluorescence and OCT angiography to structural OCT led to reclassification of 31 eyes to a more severe category. Systemic and ocular factors evaluated, including SFCT, were not associated with disease severity. Comparison of PPE, CSC and PNV eyes showed no significant difference in OCT features of retinal pigment epithelial (RPE) dysfunction, but disruption of the ellipsoid zone (PPE 30.5% vs CSC 70.7% vs PNV 60%, pConclusionsThese cross-sectional associations suggest pachychoroid disease manifestations may reflect progressive decompensation from the choroid to the RPE then retinal layers. Planned follow-up of this cohort will be beneficial in clarifying the natural history of the pachychoroid phenotype.

In this paper, the total eclipsing binary WISE J185503.7+592234 (hereinafter J185503), whose mass ratio is around the mass ratio limit, was observed and investigated for the first time. The stellar atmospheric parameters of the primary (more massive) component were calculated by the spectral fitting, and the following results are obtained: Teff = 5747 ± 25 K, [Fe/H] = −0.16 ± 0.04 dex, logg = 4.78 ± 0.05 cm s−2. Although J185503 has a very small amplitude (∼ 0.17 mag in V band) and a short period (0.2800782 d), its light curves exhibit total eclipses (eclipse duration: ∼ 40 min, which is about 0.1 phase). The light curves derived from TESS exhibit some unusual behaviour, such as inversion of the O’Connell effect, exchange of occultation, and transit depths. Photometric solutions obtained from the multiband observations suggest that J185503 has a particularly low mass ratio (q = 0.0514) and a moderate contact degree of $26{{\ \rm per\ cent}}$. Based on 103 newly determined times of minimum spanning 14 yr, a secular period decrease was found, which is calculated to be dP/dt = −2.24 × 10−7 d yr−1. Through analysing the instability criterion, such as the instability separation, the instability mass ratio, and the ratio of spin angular momentum (Jspin) to the orbital angular momentum (Jorb), J185503 can be regarded as a progenitor of luminous red novae.

Objective: To observe Paeonol effects on repair of cerebral cortex in young rats with CP. Methods: Dividing CP model rats as Model and Pae groups, and a sham operation control group was set up. Using Nissl staining to evaluate morphology and number of cortical neurons in young rats, and to determine the protein of BDNF/TrkB in peripheral serum and cerebral cortex. Results: The number of normal morphological neurons in cerebral cortex of young rats in Pae group were more than that of Model group (P < 0.01). BDNF and TrkB concentrations were significantly up-regulation in serum in Model and Pae groups (P < 0.001), meanwhile, The BDNF and TrkB concentrations significantly up-regulated in serum in Pae group (P < 0.01). By IHC and WB assay, BDNF and TrkB protein levels were significantly up-regulation in serum in Model and Pae groups (P < 0.001), meanwhile, The BDNF and TrkB protein levels were significantly up-regulation in serum in Pae group (P < 0.01). Conclusion: Pae can all play a role in repairing cerebral cortex damage in young rats with cerebral palsy via BDNF/TrkB.

Introduction: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. Method: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. Results: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P

Background Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. Methods We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group’s definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0–2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. Results 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06–1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50–0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17–2.78). Conclusion There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

Multi-band photometric observations of 11 totally eclipsing contact binaries were carried out. Applying the Wilson–Devinney program, photometric solutions were obtained. There are two W-subtype systems, which are CRTS J133031.1+161202 and CRTS J154254.0+324652, and the rest of the systems are A-subtype systems. CRTS J154254.0 + 324652 has the highest fill-out factor with 94.3 per cent, and the lowest object is CRTS J155009.2 + 493639 with only 18.9 per cent. The mass ratios of the 11 systems are all less than 0.1, which means that they are extremely low-mass ratio binary systems. We performed period variation investigation and found that the orbital periods of three systems decrease slowly, which may be caused by the materials may transfer from the primary component to the secondary component, and those of six systems increase slowly, which indicates that the materials may transfer from the secondary component to the primary component. LAMOST low-resolution spectra of four objects were analysed, and using the spectral subtraction technique, Hα emission line was detected, which means that the four objects exhibit chromospheric activity. In order to understand their evolutionary status, the mass–luminosity and mass–radius diagrams were plotted. The two diagrams indicate that the primary component is in the main sequence evolution stage, and the secondary component is above TAMS, indicating that they are over-luminous. To determine whether the 11 systems are in a stable state, the ratio of spin angular momentum to orbital angular momentum (Js/Jo) and the instability parameters were calculated, and we argued that CRTS J234634.7 + 222824 is on the verge of a merger.

In this review, the most recent development in healable polymers with dynamic B–O links is discussed, taking readers through the concept and features of dynamic B–O linkages to explore their advanced functionalities and emerging applications.

A novel multienzyme cascade was designed for the regio- and stereo-selective amination of renewable fatty acids to value-added d-amino acids.

This sensor was used to detect the concentration of Cu2+ ions in lake water with satisfactory results. The nanosensor was developed by using a simple mixture of AuNCs and WS2-QDs without necessary fabrication of silica microspheres.

One-dimensional (1D)/two-dimensional (2D) heterostructures offer attractive opportunities for developing high-performance gas sensors.