STK10 mutations block erythropoiesis in acquired pure red cell aplasia via impairing ribosome biogenesis.

Acquired pure red cell aplasia (PRCA) is anemia associated with the absence of erythroblasts and is characterized by persistent and easy recurrence. However, the underlying mechanisms of acquired PRCA remain obscure, and the role of gene mutations in the pathogenesis of acquired PRCA is not fully characterized. In the present study, we detected thirty newly diagnosed patients with acquired PRCA using whole exome sequencing, and a potential role for STK10 in acquired PRCA was uncovered. The mRNA levels of STK10 in three patients with STK10 mutations were decreased. These three patients had a poor response to immunosuppressive therapy and two died in the follow-up period. Here we report that knockdown of STK10 inhibits erythroid differentiation and promotes apoptosis of K562 cells. We show that knockdown of STK10 resulted in inhibition of ribosome biogenesis and reduced ribosome levels in K562 cells. We also show that the p53 signaling pathway is activated by knockdown of STK10. Our results imply that ribosome biogenesis downregulation together with pathological p53 activation prevents normal erythropoiesis. Our study uncovers a new pathophysiological mechanism leading to acquired PRCA driven by STK10 mutations.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Ductal Hyperkeratinization and Acinar Renewal Abnormality: New Concepts on Pathogenesis of Meibomian Gland Dysfunction.

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

The Effects of Acid and Water in the Formation of Anodic Alumina: DFT and Experiment Study.

The DFT method is employed to study the adsorption and reaction behaviors of HC2O4-, H2PO4-, HSO4- and H2O on neutral and anodic aluminum slabs. With the exception of adsorption, the three acid radicals can successively take the two H atoms from the adsorbed H2O on the anodic aluminum slabs, which is the key step of the formation of anodic alumina. The dehydrogenation reaction is dominated by the Coulombic interaction of O and H, respectively belonging to acid radicals and the adsorbed H2O or OH, rather than by the interaction of electronic orbits located on the two kinds of atoms. The experiment of anodic polarization of aluminum verifies the calculation result well.

Assessment of the influence of keratometry on intraocular lens calculation formulas in long axial length eyes.

PURPOSE: Hyperopic surprises tend to occur in axial myopic eyes and other factors including corneal curvature have rarely been analyzed in cataract surgery, especially in eyes with long axial length (≥ 26.0 mm). Thus, the purpose of our study was to evaluate the influence of keratometry on four different formulas (SRK/T, Barrett Universal II, Haigis and Olsen) in intraocular lens (IOL) power calculation for long eyes. METHODS: Retrospective case series. A total of 180 eyes with axial length (AL) ≥ 26.0 mm were divided into 3 keratometry (K) groups: K ≤ 42.0 D (Flat), K ≥ 46.0 D (Steep), 42.0 < K < 46.0 D (Average), and all the eyes were underwent phacoemulsification cataract surgery with Rayner (Hove, UK) 920H IOL implantation. Prediction errors (PE) were compared between different formulas to assess the accuracy of different formulas. Multiple regression analysis was performed to investigate factors associated with the PE. RESULTS: The mean absolute error was higher for all evaluated formulas in Steep group (ranging from 0.66 D to 1.02 D) than the Flat (0.34 D to 0.67 D) and Average groups (0.40 D to 0.74D). The median absolute errors predicted by Olsen formula were significantly lower than that predicted by Haigis formula (0.42 D versus 0.85 D in Steep and 0.29 D versus 0.69 D in Average) in Steep and Average groups (P = 0.012, P < 0.001, respectively). And the Olsen formula demonstrated equal accuracy to the Barrett II formula in Flat and Average groups. The predictability of the SRK/T formula was affected by the AL and K, while the predictability of Olsen and Haigis formulas was affected by the AL only. CONCLUSIONS: Steep cornea has more influence on the accuracy of IOL power calculation than the other corneal shape in long eyes. Overall, both the Olsen and Barrett Universal II formulas are recommended in long eyes with unusual keratometry.

Phlegmasia Cerulea Dolens in the Upper Extremity: A Case Report and Literature Review.

Phlegmasia cerulea dolens (PCD) is a rare condition characterized by deep venous thrombosis with gangrene. It can result in critically severe edema that affects the blood supply to the limbs. PCD generally occurs in the lower rather than upper extremity. We herein present a case report of upper extremity PCD and discuss thrombophilia secondary to low protein S activity as the main cause. Catheter-directed thrombolysis via the occluded end of the artery may be one of the best treatment methods for PCD.

Fully automated segmentation in temporal bone CT with neural network: a preliminary assessment study.

BACKGROUND: Segmentation of important structures in temporal bone CT is the basis of image-guided otologic surgery. Manual segmentation of temporal bone CT is time- consuming and laborious. We assessed the feasibility and generalization ability of a proposed deep learning model for automated segmentation of critical structures in temporal bone CT scans. METHODS: Thirty-nine temporal bone CT volumes including 58 ears were divided into normal (n = 20) and abnormal groups (n = 38). Ossicular chain disruption (n = 10), facial nerve covering vestibular window (n = 10), and Mondini dysplasia (n = 18) were included in abnormal group. All facial nerves, auditory ossicles, and labyrinths of the normal group were manually segmented. For the abnormal group, aberrant structures were manually segmented. Temporal bone CT data were imported into the network in unmarked form. The Dice coefficient (DC) and average symmetric surface distance (ASSD) were used to evaluate the accuracy of automatic segmentation. RESULTS: In the normal group, the mean values of DC and ASSD were respectively 0.703, and 0.250 mm for the facial nerve; 0.910, and 0.081 mm for the labyrinth; and 0.855, and 0.107 mm for the ossicles. In the abnormal group, the mean values of DC and ASSD were respectively 0.506, and 1.049 mm for the malformed facial nerve; 0.775, and 0.298 mm for the deformed labyrinth; and 0.698, and 1.385 mm for the aberrant ossicles. CONCLUSIONS: The proposed model has good generalization ability, which highlights the promise of this approach for otologist education, disease diagnosis, and preoperative planning for image-guided otology surgery.

Gene mutation profile in patients with acquired pure red cell aplasia.

Acquired pure red cell aplasia (PRCA) is a disorder characterized by normocytic anemia associated with reticulocytopenia and an absence of erythroblasts. The gene mutation profile in acquired PRCA is not defined yet. In this study, we aimed to identify the gene mutation spectrum of patients with acquired PRCA and the correlation between gene mutations and response to immunosuppressive therapy (IST). Thirty newly diagnosed acquired PRCA patients were enrolled in this study, and then whole-exome sequencing were performed among these patients and a panel with 93 candidate genes which associated with other bone marrow failure for the following analysis. Subsequently patients were treated with IST for at least 2 years. When treated with IST, there were thirteen complete response, ten partial response (ORR 76.7%), and seven no response at a medium of 8 (6-10) months. Totally twenty-three mutations in fifteen genes were detected in sixteen patients (53%). The mutated genes were associated with transcription, signal transduction, and epigenetic regulation pathways. The most frequent transitions in the point mutations were C > T. Age, gender, hemoglobin level at diagnosis, and gene mutation or not did not influence the response to IST. However, although patients with BCOR or BCORL1 mutations had a similar response to IST compared with those without mutation (P = 0.235), they had a better response than those with other gene mutations (P = 0.0193). In conclusion, patients with acquired PRCA may have clonal gene mutations. The patients with BCOR and BCORL1 mutations may suggest a better response to IST compared with those with other mutations.

The effectiveness and safety of beta antagonist in burned patients: A systematic review and meta-analysis.

Beta antagonist is one of the most effective and the least toxic pharmacological treatments to attenuate the raised catecholamine effects for burned patients. To evaluate the effectiveness and safety of beta blocker compared with placebo or usual care in burned patients, a meta-analysis of randomised controlled trials (RCTs) was conducted. We searched the database of PubMed, Embase, the Cochrane Library, and Web of Science to 10 April 2020. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We performed the meta-analysis using a random-effect model. A total of 12 RCTs were included in the study, including 1887 patients. Propranolol-treated patients have a decrease in length of hospital stay in adults (weighted mean difference [WMD] = -9.06, 95% CIs = [-12.88, -5.24]) and prepare time of graft (WMD = -7.88, 95% CIs = [-12.27, -3.50]). Similarly, the use of propranolol could significantly decrease heart rate (WMD = -15.16, 95% CIs = [-20.37, -9.94]), rate pressure product (WMD = -1.32, 95% CIs = [-1.67, -0.97]), and mean arterial pressure (WMD = -2.75, 95% CIs = [-4.23, -1.26]). Moreover, there is no significant difference between propranolol and placebo with respect to mortality (risk difference [RD] = 0.00, 95% CIs [-0.03, 0.04]), sepsis (RD = -0.03, 95% CIs [-0.09, 0.03]), and events of post-traumatic stress disorder (PTSD) and acute stress disorder (RD = -0.01, 95% CIs [-0.07, 0.05]), and also, there is no significant difference in subgroup analysis based on age. The use of beta antagonist in burned patients does reduce length of hospital stay in adults, shorten the preparation time for graft, and reduce heart burden, without increasing mortality, sepsis, or PTSD compared with those who had usual care or placebo. So beta antagonist can be considered as an appropriate treatment strategy in burned patients. More prospective, randomised-controlled, multi-centre studies were needed to define their place in therapeutic algorithms.

Transcriptomic analysis reveals Apis mellifera adaptations to high temperature and high humidity.

Temperature and humidity are the most important factors affecting the growth, reproduction, and survival of bees. Apis mellifera are important pollinating bees that are widely used in agricultural systems. However, the higher temperatures and humidity in greenhouses are not conducive to the survival of bees. Although previous research has revealed the behavioral responses and physiological mechanisms of honeybees to adapt to high temperature and humidity, there are few data on the exact molecular mechanisms involved. In our study, we investigated gene expression in A. mellifera under different temperature and humidity treatments, using transcriptomic analysis to identify differentially expressed genes (DEGs) and relevant biological processes. Based on the transcriptomic results, we selected several genes with significant differences in expression, and detected the expression patterns of these genes at different temperatures or humidity or different treatment times by q-RT PCR. In the high temperature treatments, 434 DEGs were identified; in the high humidity treatments, 86 DEGs were identified; in the combined high temperature and humidity treatments, 266 DEGs were identified. Analysis results showed that DEGs were enriched in pathways related to amino acid and fatty acid biosynthesis and metabolism under each treatment. In addition, heat shock proteins, zinc finger proteins, serine/threonine-protein kinases, and antioxidase were differentially expressed between the different treatments. The results of the q-RT PCR showed that the expression levels of these genes increased with increasing temperature and over treatment time. Our findings provide a general expression profile of the adaptive expression of heat-resistance genes responding to high temperature and high humidity in A. mellifera, including the expression patterns of several DEGs. Our data provide a basis for future research on the mechanisms underlying the adaptation of insects to high temperature and humidity.

Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus.

Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and obvious bone marrow erythroblastic cells decreased. Some patients are refractory or intolerant to the first-line therapy (cyclosporine A with/without steroids). The effects of the second-line therapy are not satisfactory and sometimes not available. In this study, we analyzed the efficacy and side effect of sirolimus on refractory/relapsed aPRCA and investigated the possible mechanism of sirolimus on immune regulation. Twenty-one patients with refractory/relapsed aPRCA were enrolled in this study and were administered with sirolimus. Totally, 76.2% of patients responded to the sirolimus with 42.9% complete response during the experimental period. The median time for reaction was 4 months. Side effects were tolerable including infections; mild oral mucositis; sinus tachycardia, the increase of creatinine, transaminase, triglyceride, or cholesterol; and thrombocytopenia. Most patients stayed in remission or remained stable during the follow-up period. Early drug withdrawal may lead to quick relapse. Compared with healthy control, Treg levels in patients with aPRCA reduced significantly before sirolimus but recovered after successful treatment. Level of Treg cells correlated with hemoglobin level after effective sirolimus treatment. Thus, sirolimus was effective and tolerable for refractory/relapsed aPRCA. Effective sirolimus treatment may lead to the upregulation of Treg cells which may partly explain the underlying mechanism.

New Concept of X-Ray Repair Cross-Complementing Groups 1 Polymorphisms and Gynecologic Cancer Risk.

BACKGROUND: Several meta-analyses have been conducted to examine the possible link between X-ray repair cross-complementing groups 1 (XRCC1) Arg399Gln polymorphism and cervical cancer risk. However, the results are controversial. Therefore, we carried out a more comprehensive meta-analysis to examine whether XRCC1 polymorphisms are associated with general gynecologic cancer risk. METHODS: Twenty studies, comprising 4,230 cases and 5,458 controls that included analyses of XRCC1 polymorphisms (Arg194Trp, Arg280His, or Arg399Gln) were included in our study. RESULTS: Overall, no significant association between any of the studied XRCC1 polymorphisms and gynecologic cancer risk was observed. However, in further stratified analyses, the Arg399Gln was definitely associated with increased gynecologic cancer risk in Asians (A vs. G: OR 1.24; 95% CI 1.02-1.53), which was also associated with increased cervical cancer risk (A vs. G: OR 1.20; 95% CI 1.00-1.44). Similarly, the Arg194Trp was significantly associated with increased gynecologic cancer risk in Asians (TT vs. CC: OR 1.87; 95% CI 1.02-3.42) and endometrial cancer (T vs. C: OR 1.45; 95% CI 1.05-2.02). CONCLUSIONS: These findings provided evidence that XRCC1 Arg399Gln and Arg194Trp variants may modify the susceptibility to gynecologic cancers based on ethnicity and type. Further studies with large sample size are warranted to extend our findings.

Observational Monitoring of Patients with Aplastic Anemia and Low/Intermediate-1 Risk of Myelodysplastic Syndromes Complicated with Iron Overload.

BACKGROUND: This study focuses on the iron overload (IOL) of patients with transfused aplastic anemia (AA) or a low/intermediate-1 risk of myelodysplastic syndrome (MDS). METHODS: Ninety-two AA or MDS patients with IOL were prospectively recruited. Clinical data were collected every 6 months, and organ magnetic resonance imaging T2* values were collected annually. Patients with IOL were chelated. RESULTS: Serum ferritin was correlated with liver T2* and pancreatic T2* in the AA and MDS groups. Transfusion amounts were correlated with serum ferritin values, liver T2*, and pancreatic T2* in the AA group. At the 6-month and 1-year evaluations, patients with sufficient chelation experienced significant decreases in serum ferritin, and those with decreased serum ferritin experienced an obvious increase in hemoglobin. At their 1-year-follow-up, patients with adequate chelation showed significant increases in hepatic T2*, cardiac T2*, and left ventricular ejection fraction (LVEF). Patients with decreased serum ferritin (including those without chelation) experienced an increase in hemoglobin, hepatic T2*, cardiac T2*, and LVEF. CONCLUSION: The transfusion amount was more reliable at predicting IOL in patients with AA than in those with MDS. Adequate iron chelation can decrease serum ferritin levels and may improve hepatic T2*, cardiac T2*, and LVEF levels. A decrease in serum ferritin, even in the absence of chelation, may also benefit patients.

Corpus Callosotomy for Patients With Intractable Seizures: An Insight Into the Rapid Relapse.

It is well known that corpus callosotomy (CC) can bring a favorable seizure control outcome for disabling generalized seizures, but the complete remission rate achieved by CC is rarely reported, and the postoperative relapse pattern is still not clear. In this study, the authors reviewed patients with medically refractory epilepsy who were suffering disabling seizures, including drop attacks, generalized tonic-clonic seizures (GTCS), tonic seizures, atonic seizures, atypical absences, and complex partial seizures. The patients underwent anterior two third or complete CC in our hospital. Seizure control outcome was evaluated postoperatively at 2 weeks, 1 month, 3 months, 6 months, thereafter, at yearly intervals. Seizure-free or >90% reduction was considered to be satisfactory. There were 14 patients with mean age 11.00 ±â€Š6.34 at surgery. Of all the patients, 6 patients underwent anterior two third CC, and the other 8 patients underwent complete CC. All the patients were postoperatively followed up for at least 1 year. Four patients (28.57%) were free of all seizure types in the first year after surgery. Among the 9 patients with follow-up longer than 3 years, 2 patients (22.22%) were free of all seizure types. In the first 3 months after surgery, more than half of the seizure free patients (55.56%) relapsed with the same seizure types as preoperatively. Although after that, there was only 1 patient relapsed. Of all the seizure types, CC achieved the most favorable seizure outcome in drop attacks. In conclusion, CC could achieve complete seizure remission in a small portion of selected candidates. Exploration of the relapse mechanism will contribute to improve the seizure outcome following CC.

Correlation of Eosinophils and Type 2 Inflammatory Mediators with Osteitis in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

Comparison of Predictability in Vault Using NK Formula and KS Formula for the Implantable Collamer Lens Surgery.

Background: This study aims to investigate the agreement between the NK and KS formulas in predicting the vault after implantation of an EVO-implantable collamer lens (ICL). Methods: This retrospective study included 106 eyes of 57 patients who underwent ICL-V4c implantation. Preoperative vault prediction was conducted by utilizing the NK and KS formulas, with postoperative measurements by anterior segment optical coherence tomography (AS-OCT) at one month. The analysis focused on the consistency between predicted and achieved vaults, as well as the correlation between the achieved vault and various biometric parameters. Results: The mean achieved vault was 605.25 ± 212.72 µm, which was significantly smaller than the predicted vaults of 710.08 ± 195.08 and 673.80 ± 212.76 µm, using the NK and KS formulas, respectively (P < 0.05). The mean differences between the achieved vault and the predicted vault using the NK formula and KS formula were -104.82 µm (95% LoA: -600.38-391.19 µm) and -68.55 µm (95% LoA: -628.91-491.82 µm), respectively. Anterior chamber depth (ACD), vertical sulcus-to-sulcus (V-STS) diameter, and crystalline lens rise (CLR) were independent factors associated with the achieved vault (P < 0.05). The two formulas showed no statistically significant difference in absolute prediction error (APE). Conclusion: The NK formula exhibited superior consistency and low predictive error compared to the KS formula in the 12.6 mm ICL group. AS-OCT measurements overestimated the predicted ICL vault, especially in the 13.2 mm ICL size selection. Relying solely on the NK or KS formulas for predicting vaults before ICL surgery is not recommended.

Valvar bypass surgery to ameliorate persistent lower limb edema caused by post-thrombotic syndrome: a case report and literature review.

Obstruction and/or reflux compromise during venous emptying can facilitate different pathophysiologies in chronic venous insufficiency (CVI). We present a patient with persistent lower limb CVI edema caused by post-thrombotic syndrome (PTS), who responded well to femoral vein valve therapy via axillary vein bypass after unsuccessful valvuloplasty, and led a normal life. During a 12 month observation period, bridging vessels completely restored original anatomical structures. In a literature study, no similar surgeries were reported, but we show that this operation may be feasible in selected patients.

Preliminary Study on the Pathogenic Mechanism of Jujube Flower Disease in Honeybees (Apis mellifera ligustica) Based on Midgut Transcriptomics.

Honeybees are prone to poisoning, also known as jujube flower disease, after collecting nectar from jujube flowers, resulting in the tumultuous demise of foragers. The prevalence of jujube flower disease has become one of the main factors affecting the development of the jujube and beekeeping industries in Northern China. However, the pathogenic mechanisms underlying jujube flower disease in honeybees are poorly understood. Herein, we first conducted morphological observations of the midgut using HE-staining and found that jujube flower disease-affected honeybees displayed midgut damage with peritrophic membrane detachment. Jujube flower disease was found to increase the activity of chitinase and carboxylesterase (CarE) and decrease the activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of CYP450 in the honeybee midgut. Transcriptomic data identified 119 differentially expressed genes in the midgut of diseased and healthy honeybees, including CYP6a13, CYP6a17, CYP304a1, CYP6a14, AADC, and AGXT2, which are associated with oxidoreductase activity and vitamin binding. In summary, collecting jujube flower nectar could reduce antioxidant and detoxification capacities of the honeybee midgut and, in more severe cases, damage the intestinal structure, suggesting that intestinal damage might be the main cause of honeybee death due to jujube nectar. This study provides new insights into the pathogenesis of jujube flower disease in honeybees.

Selective biosynthesis of a rhamnosyl nosiheptide by a novel bacterial rhamnosyltransferase.

Nosiheptide (NOS) is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. The hydroxyl group of 3-hydroxypyridine in NOS has been identified as a promising site for modification, which we therefore aimed to rhamnosylate. After screening, Streptomyces sp. 147326 was found to regioselectively attach a rhamnosyl unit to the 3-hydroxypyridine site in NOS, resulting in the formation of a derivative named NOS-R at a productivity of 24.6%. In comparison with NOS, NOS-R exhibited a 17.6-fold increase in aqueous solubility and a new protective effect against MRSA infection in mice, while maintaining a similar in vitro activity. Subsequently, SrGT822 was identified as the rhamnosyltransferase in Streptomyces sp. 147326 responsible for the biosynthesis of NOS-R using dTDP-L-rhamnose. SrGT822 demonstrated an optimal reaction pH of 10.0 and temperature of 55°C, which resulted in a NOS-R yield of 74.9%. Based on the catalytic properties and evolutionary analysis, SrGT822 is anticipated to be a potential rhamnosyltransferase for use in the modification of various complex scaffolds.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.