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Yan-Li Du,1 Chun-Hua Ma,1 Yu-Feng Liao,1 Lu Wang,2 Ya Zhang,1 Geng Niu3 1School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, 518055, Guangdong, People’s Republic of China; 2Delivery Center, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, 518028, Guangdong, People’s Republic of China; 3Shenzhen Elderly Healthcare College, Shenzhen Polytechnic, Shenzhen, Guangdong, 518055, People’s Republic of ChinaCorrespondence: Geng NiuShenzhen Elderly Healthcare College, Shenzhen Polytechnic, Shenzhen, 518055, Guangdong, People’s Republic of ChinaTel +86 755 86379018Fax +86 755 26731867Email niugeng_dr@163.comObjective: To evaluate the effectiveness of a clinical scenario simulation method among nursing students for assessing the risk of patients developing pressure ulcers compared with the traditional didactic method.Methods: This experimental study was a controlled trial with single-blind assessments. Nursing students (n = 47) were randomly assigned to either a control or an experimental group. The control group (n = 21) was instructed using traditional didactic methods that only delivered knowledge of pressure ulcers, while the experimental group (n = 26) received a clinical scenario simulation-based method for cultivating the competence to assess the risk of pressure ulcers. Participants underwent pre- and post-intervention based on the objective structured clinical examination (OSCE) comprising objective performance criteria. Data were analyzed using a t-test in the SPSS Statistics software program at a significance level of 0.05.Results: No significant differences were observed regarding age or the mean scores of the OSCE in pre-intervention between the two groups. Following the intervention, the mean score of the experimental group’s performance was higher (29.04 ± 6.00) compared with the control group (12.38 ± 4.15) (P = 0.000). There were statistical differences between the two groups. Nursing students in the clinical scenario simulation group performed significantly better in recognizing and assessing the risk of pressure ulcers.Conclusion: This study demonstrates that a clinical scenario simulation approach is more effective than employing the traditional didactic method for cultivating students’ assessment ability regarding pressure ulcers. This student-centered, clinical scenario simulation method can help to effectively develop students’ competency in recognizing and assessing the risk of pressure ulcers, thereby providing a solid foundation for their clinical practice towards enhanced patient safety.Keywords: pressure ulcer, clinical scenario simulation, didactic method, patient safety, competence, systematic assessment

In this proceeding, we review our recent work using deep convolutional neural network (CNN) to identify the nature of the QCD transition in a hybrid modeling of heavy-ion collisions. Within this hybrid model, a viscous hydrodynamic model is coupled with a hadronic cascade “after-burner”. As a binary classification setup, we employ two different types of equations of state (EoS) of the hot medium in the hydrodynamic evolution. The resulting final-state pion spectra in the transverse momentum and azimuthal angle plane are fed to the neural network as the input data in order to distinguish different EoS. To probe the effects of the fluctuations in the event-by-event spectra, we explore different scenarios for the input data and make a comparison in a systematic way. We observe a clear hierarchy in the predictive power when the network is fed with the event-by-event, cascade-coarse-grained and event-fine-averaged spectra. The carefully-trained neural network can extract high-level features from pion spectra to identify the nature of the QCD transition in a realistic simulation scenario.

Using deep convolutional neural network (CNN), the nature of the QCD transition can be identified from the final-state pion spectra from hybrid model simulations of heavy-ion collisions that combines a viscous hydrodynamic model with a hadronic cascade “after-burner”. Two different types of equations of state (EoS) of the medium are used in the hydrodynamic evolution. The resulting spectra in transverse momentum and azimuthal angle are used as the input data to train the neural network to distinguish different EoS. Different scenarios for the input data are studied and compared in a systematic way. A clear hierarchy is observed in the prediction accuracy when using the event-by-event, cascade-coarse-grained and event-fine-averaged spectra as input for the network, which are about 80%, 90% and 99%, respectively. A comparison with the prediction performance by deep neural network (DNN) with only the normalized pion transverse momentum spectra is also made. High-level features of pion spectra captured by a carefully-trained neural network were found to be able to distinguish the nature of the QCD transition even in a simulation scenario which is close to the experiments.

We revisit the calculation of multiple parton scattering of a heavy quark in nuclei within the framework of recently improved high-twist factorization formalism, in which gauge invariance is ensured by a delicate setup of the initial partons' transverse momenta. We derive a new result for medium modified heavy quark fragmentation functions in deeply inelastic scattering. It is consistent with the previous calculation of light quark energy loss in the massless limit, but leads to a new correction term in the heavy quark case, which vanishes in the soft gluon radiation limit. We show numerically the significance of the new correction term in the calculation of heavy quark energy loss as compared to previous studies and with soft gluon radiation approximation.

Background: This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021., Methods: The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty., Results: The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002)., Conclusions: The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty., (© 2024. The Author(s).)

Background: Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3-E1 cells in vitro., Results: Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress., Conclusion: Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Traumatic main bronchus rupture is a relatively rare injury in thoracic trauma, which is extremely critical, with a mortality rate as high as 70% - 80%. The complete rupture and displacement of the traumatic cervical trachea can lead to asphyxia, hypoxia, and cardiac arrest, even death of the patient in a short time. We performed emergency surgery with the support of extracorporeal membrane oxygenation for a case of traumatic cervical tracheal trunk complete rupture and displacement combined with cardiac arrest and achieved a successful rescue. We summarized our experience and found that timely surgical reconstruction of the airway is the key to increasing the traumatic main bronchus rupture survival of patients., (Copyright © 2024. Production and hosting by Elsevier B.V.)

The anti- Clostridium difficile infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by Micromonosporaceae , such as Actinoplanes deccanensis , Dactylosporangium aurantiacum , and Micromonospora echinospora . In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered Streptomyces albus D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain Actinoplanes deccanensis YP-1 with higher strain stability and growth rate. This study developed an enhanced chassis strain, and for the first time, achieved the heterologous synthesis of fidaxomicin through a combinatorial metabolic engineering strategy., Competing Interests: All authors have approved the manuscript for submission and we declare that we have no competing interests., (© 2024 The Authors.)

Structural motifs containing nitrogen-nitrogen (N-N) bonds are prevalent in a large number of clinical drugs and bioactive natural products. Hydrazine (N 2 H 4 ) serves as a widely utilized building block for the preparation of these N-N-containing molecules in organic synthesis. Despite its common use in chemical processes, no enzyme has been identified to catalyze the incorporation of free hydrazine in natural product biosynthesis. Here, we report that a hydrazine transferase catalyzes the condensation of N 2 H 4 and an aromatic polyketide pathway intermediate, leading to the formation of a rare N-aminolactam pharmacophore in the biosynthesis of broad-spectrum antibiotic albofungin. These results expand the current knowledge on the biosynthetic mechanism for natural products with N-N units and should facilitate future development of biocatalysts for the production of N-N-containing chemicals.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC)., Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections., Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P  = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P  = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P  = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P  = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P  = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P  = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P  = 0.012). Besides, the area under the ROC curve was 0.889., Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Chronic wounds are a common and costly health issue affecting millions of individuals in the United States, particularly those with underlying conditions such as diabetes, venous insufficiency, and peripheral artery disease. When standard treatments fail, advanced wound care therapies, such as skin substitutes, are often applied. However, the clinical effectiveness, indications, and comparative benefits of these therapies have not been well established. In this study, we report on the usage of both acellular and cellular, single and bilayer, natural and synthetic, dermal, and epidermal skin substitutes in a VA hospital system. We performed a retrospective chart review to understand the ordering and usage patterns of advanced wound therapies for patients with chronic wounds at the VA Northern California Health Care System. We examined types of products being recommended, categories of users recommending the products, indications for orders, and rate of repeated orders. Neuropathic, venous, or pressure ulcers were the main indications for using advanced wound matrices. Only 15.6% of patients for whom the matrices were ordered had supporting laboratory tests. Exactly 34.3% of the ordered matrices were not applied. And the use of wound matrices resulted in increased costs per patient visit of $1018-$3450. Our study sheds light on the usage patterns of these therapies in a VA healthcare facility and highlights the need for more robust evidence-based studies to determine the true benefits, efficacy, and cost-effectiveness of these innovative treatment options., (© 2024 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

The biological signaling molecule nitric oxide (NO) has recently emerged as a metabolic precursor for the creation of microbial natural products with diversified structures and biological activities. Within the biosynthetic gene clusters (BGCs) of these compounds, genes associated with NO production pathways have been pinpointed. In this study, we employ a nitric oxide synthase (NOS)-guided genome mining strategy for the targeted discovery of NO-derived bacterial natural products and NO-utilizing biocatalysts. We show that a conserved NOS-containing BGC, distributed across several actinobacterial genomes, is responsible for the biosynthesis of lajollamycin, a unique nitro-tetraene-containing antibiotic whose biosynthetic mechanism remains elusive. Through a combination of in vivo and in vitro studies, we unveil the first cytochrome P450 enzyme capable of catalyzing olefin nitration in natural product biosynthesis. These results not only expand the current knowledge about biosynthetic nitration processes but also offer an efficient way for targeted identification of NO-utilizing metabolic pathways and novel nitrating biocatalysts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

An effective Ag(I)-mediated annulation of 2-(2-enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2 H -pyrrol-3-yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2 H -pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.

Azoxy compounds exhibit a wide array of biological activities and possess distinctive chemical properties. Although there has been considerable interest in the biosynthetic mechanisms of azoxy metabolites, the enzymatic basis responsible for azoxy bond formation has remained largely enigmatic. In this study, we unveil the enzyme cascade that constructs the azoxy bond in valanimycin biosynthesis. Our research demonstrates that a pair of metalloenzymes, comprising a membrane-bound hydrazine synthase and a nonheme diiron azoxy synthase, collaborate to convert an unstable pathway intermediate to an azoxy product through a hydrazine-azo-azoxy pathway. Additionally, by characterizing homologues of this enzyme pair from other azoxy metabolite pathways, we propose that this two-enzyme cascade could represent a conserved enzymatic strategy for azoxy bond formation in bacteria. These findings provide significant mechanistic insights into biological N-N bond formation and should facilitate the targeted isolation of bioactive azoxy compounds through genome mining.

Objective: To evaluate the early efficacy and safety of transnasal endoscopic decompression in the annulus of zinn (AZ) region for refractory dysthyroid optic neuropathy (DON) and to preliminarily analyze the correlated factors of postoperative visual function outcome. Methods: From July 2021 to January 2023, 35 patients (56 eyes) with DON who received AZ area decompression in Peking University Third Hospital were included retrospectively, including 9 males (13 eyes) and 26 females (43 eyes), aging (52.2±12.0) years. Among them, 35 eyes underwent two-wall (medial and inferior) orbital decompression using an endonasal endoscopic approach, while 21 eyes received three-wall (medial, lateral, and inferior) orbital decompression through a combined approach. Key parameters such as best corrected visual acuity (BCVA), visual field (MD value), eyeball prominence, intraocular pressure, and complications were recorded. Postoperative data were collected one month after surgery. The statistical analysis was performed using paired t -test and Spearman correlation analysis. Results: Significant outcomes were observed post surgery in BCVA, visual field, intraocular pressure and proptosis ( t value was 8.37, 6.17, 4.50, and 9.20, respectively, all P <0.001). The reduction in proptosis was statistically significant between the 2-wall and 3-wall orbital decompression groups ( t =-2.82, P =0.007). Changes in BCVA, visual field, and intraocular pressure before and after surgery was greater in the 3-wall orbital decompression group compared to 2-wall orbital decompression group, although the difference was not statistically significant (all P >0.05). Change in postoperative visual acuity and visual field was significantly positively correlated with preoperative visual acuity and preoperative visual field (all P <0.001). Similarly, change in intraocular pressure and proptosis was positively correlated with preoperative intraocular pressure and preoperative protrusion (all P <0.001). Preoperative diplopia was reported in seven patients (20.0%), and two new cases (5.7%) were noted post-operation, which resolved within 3 months after surgery. Conclusions: Endoscopic endonasal decompression of the AZ area is a safe and effective surgical treatment for DON, with notable improvements in BCVA. Furthermore, three-orbital wall decompression seems to yield better outcomes in terms of eye retraction.

Purpose: Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured out a method to isolate the MG ducts and established a novel system to culture the human meibomian gland ductal cells (HMGDCs) for investigating the process of MGD., Methods: The MG ducts were obtained from the eyelids of recently deceased donors and subjected to enzymatic digestion. The acini were then removed to isolate independent ducts. These MG ducts were subsequently cultivated on Matrigel-coated wells and covered with a glass plate to obtain HMGDCs. The HMGDCs were further cultivated until passage 2, and when they reached 60% confluence, they were treated with IL-1β and rosiglitazone for a duration of 48 hours. Immunofluorescence staining and Western blot techniques were employed to identify ductal cells and analyze the effects of IL-1β on HMGDCs in an in vitro setting., Results: Ophthalmic micro-forceps and insulin needles can be employed for the purpose of isolating ducts. Within this particular culture system, the rapid expansion of HMGDCs occurred in close proximity to the duct tissue. MG ducts specifically expressed keratin 6 (Krt6) and hardly synthesized lipids. Furthermore, the expression of Krt6 was significantly higher (P < 0.0001) in HMGDCs compared to human meibomian gland cells. Upon treatment with IL-1β, HMGDCs exhibited an overexpression of keratin 1, which was effectively blocked by the administration of rosiglitazone., Conclusions: The present study successfully isolated human MG ducts and cultured HMGDCs, providing a valuable in vitro model for investigating the mechanism of MGD. Additionally, the potential therapeutic efficacy of rosiglitazone in treating hyperkeratinization of ducts in patients with MGD was identified.

Background: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown., Methods: In vitro , hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot., Results: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC., Conclusions: These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling., Competing Interests: None., (© 2023 JGC All rights reserved; www.jgc301.com.)

Purpose: To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations in fungal keratitis (FK)., Methods: In this non-comparative, retrospective case series, 16 participants of corneal perforation in FK were successfully treated by a combination of multilayer AMT and bipedicle conjunctival flap with partial tenon's capsule. Corneal healing, recurrence of FK, visual acuity, and relevant complications were reported as outcome measures., Results: Sixteen patients (13 male, 3 female) had a mean age of 58.8 ± 10.3 (range 29-72) years. The mean diameter of corneal perforation was 1.9 ± 0.7 (range 0.5-2.8) mm. Corneal perforations healed and all the patients preserved their eyeballs. During the 11.0 ± 4.4 (range 6-18) months of follow-up, there was no recurrence of FK in any of these cases. Visual acuity improved in 15 eyes (93.8 %) and remained unchanged in 1 patient (6.3 %) who had no light perception when first admitted. All 6 patients who accepted secondary keratoplasty showed improved best corrected visual acuity of more than 4 lines. The most frequently found fungi were Aspergillus species (6 of 16, 37.5 %) and Fusarium species (4 of 16, 25.0 %), followed by 1 Scedosporium apiospermum (1 of 16, 6.3 %)., Conclusions: Combination AMT with CFCS is a safe and effective surgery for patients with corneal perforations in FK, particularly where eye banks and fresh corneas are not available. This surgery could preserve the integrity of the eyeball and avoid the recurrence of FK. Besides, it provides a greater opportunity for further optical keratoplasty., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Hydroxytryptophan serves as a chemical precursor to a variety of bioactive specialized metabolites, including the human neurotransmitter serotonin and the hormone melatonin. Although the human and animal routes to hydroxytryptophan have been known for decades, how bacteria catalyze tryptophan indole hydroxylation remains a mystery. Here we report a class of tryptophan hydroxylases that are involved in various bacterial metabolic pathways. These enzymes utilize a histidine-ligated heme cofactor and molecular oxygen or hydrogen peroxide to catalyze regioselective hydroxylation on the tryptophan indole moiety, which is mechanistically distinct from their animal counterparts from the nonheme iron enzyme family. Through genome mining, we also identify members that can hydroxylate the tryptophan indole ring at alternative positions. Our results not only reveal a conserved way to synthesize hydroxytryptophans in bacteria but also provide a valuable enzyme toolbox for biocatalysis. As proof of concept, we assemble a highly efficient pathway for melatonin in a bacterial host., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Microbial natural products have been one of the most important sources for drug development. In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming increasingly popular. Here, we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities. Our method employs uvrA -like genes as genetic markers, which have been identified in the biosynthetic gene clusters (BGCs) of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers. Through systematic genomic analysis of gifted actinobacteria genera, identification of uvrA -like gene-containing BGCs, and targeted isolation of products from a BGC prioritized for metabolic analysis, we identified a new tetracycline-type DNA intercalator timmycins. Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation., (© 2023 The Authors.)

Bacterial azapteridine-containing phytotoxin toxoflavin is a causal agent of rice grain rot. Here, we heterologously reconstitute Bukholderia toxoflavin biosynthesis in Escherichia coli and identify key pathway intermediates, including the hitherto unknown ribityl-dedimethyl-toxoflavin. Furthermore, we characterized a cofactorless oxidase that converts ribityl-dedimethyl-toxoflavin to ribose and dedimethyl-toxoflavin, the latter of which then undergoes stepwise methylations to form toxoflavin. These findings provide new insights into the biosynthetic pathways of toxoflavin and related triazine metabolites.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery., Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines., Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations., Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qin, Yang, Zheng, An, Yang, Du, Wang, Zhao, Li, Sun, Sun and Lin.)

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.

Purpose: To investigate the characteristics of in vitro culture and in vivo confocal microscopy (IVCM) in patients with fungal keratitis (FK) presented in a tertiary referral hospital in central China., Methods: In this noncomparative retrospective study, patients with the diagnosis of FK between October 2021 and November 2022 were reviewed. An IVCM and fungal culture (corneal scraping specimens) were performed, and the characteristics were analyzed., Results: During October 2021 and November 2022, 85 patients were diagnosed with FK. From 63 culture-positive cases, 8 species of fungus were identified. The proportions of isolated fungal species were Fusarium and Aspergillus equally accounting for 33.3% (21 of 63), Alternaria 9.5% (6 of 63), Curvularia 6.3% (4 of 63), Scedosporium apiospermum 6.3% (4 of 63), Paecilomyces lilacinus 3.2% (2 of 63), Exserohilum 3.2% (2 of 63), and Candida 4.8% (3 of 63), respectively. In positive culture cases, IVCM was found to be positive for hyphae or spores in 61 of 63 patients (96.8%). Different fungal species had a variety of cultural characteristics and IVCM manifestations., Conclusions: In a tertiary referral hospital in central China, Fusarium species, Aspergillus species, and Alternaria species were the 3 most common isolated fungal pathogens, and the proportion of Aspergillus species was significantly higher than that in other regions of China. Careful lesion depth examination by IVCM and OCT should be taken before lamellar keratoplasty to avoid postoperative recurrence. Identifying the IVCM image and culture characteristics will facilitate rapid diagnosis and proper treatment, but IVCM cannot yet replace fungal cultures to distinguish between different fungal species.

Background: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgeries, such as hepatectomy and liver transplantation. In recent years, several non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as factors involved in the pathological progression of HIRI. In this review, we summarized the latest research on lncRNAs, miRNAs and the lncRNA-miRNA regulatory networks in HIRI., Data Sources: The PubMed and Web of Science databases were searched for articles published up to December 2021 using the following keywords: "hepatic ischemia-reperfusion injury", "lncRNA", "long non-coding RNA", "miRNA" and "microRNA". The bibliography of the selected articles was manually screened to identify additional studies., Results: The mechanism of HIRI is complex, and involves multiple lncRNAs and miRNAs. The roles of lncRNAs such as AK139328, CCAT1, MALAT1, TUG1 and NEAT1 have been established in HIRI. In addition, numerous miRNAs are associated with apoptosis, autophagy, oxidative stress and cellular inflammation that accompany HIRI pathogenesis. Based on the literature, we conclude that four lncRNA-miRNA regulatory networks mediate the pathological progression of HIRI. Furthermore, the expression levels of some lncRNAs and miRNAs undergo significant changes during the progression of HIRI, and thus are potential prognostic markers and therapeutic targets., Conclusions: Complex lncRNA-miRNA-mRNA networks regulate HIRI progression through mutual activation and antagonism. It is necessary to screen for more HIRI-associated lncRNAs and miRNAs in order to identify novel therapeutic targets., (Copyright © 2022. Published by Elsevier B.V.)

Background: Nurses are in high-pressure, high-load, and high-risk environment for a long time, and their insomnia cannot be ignored. Insomnia not only has a negative impact on the physical and mental health of nurses, but also on the efficiency and quality of nursing work., Objective: The purpose of this study was to investigate the multiple mediating effect of psychological capital, effort-reward ratio, and overcommitment in the relationship between perceived organizational support and insomnia among Chinese nurses., Methods: A cross-sectional study has been carried out in a tertiary grade A hospital in Shandong Province, China from March 2021 to May 2021. The demographic questionnaire, Perceived Organization Support Questionnaire, Psychological Capital Questionnaire, Chinese version Effort-Reward Imbalance, Questionnaire and Athens Insomnia Scale were used for data collection. SPSS PROCESS 3.4 macro program developed by Hayes was used to test the serial multiple mediation. Descriptive analysis, independent-samples t -test, one-way analysis of variance, Pearson's correlation analyses, ordinary least-squares regression, and the bootstrap method were used for data analysis., Results: 658 valid questionnaires were collected (81.2%). Nurses' perceived organizational support was positively correlated with psychological capital ( r  = 0.455, p  < 0.001), and was significantly negatively correlated with effort-reward ratio ( r  = -0.318, p  < 0.001), overcommitment ( r  = -0.328, p  < 0.001), and insomnia ( r  = -0.358, p  < 0.001); Psychological capital was negatively correlated with effort-reward ratio (r = -0.275, p  < 0.001), overcommitment ( r  = -0.339, p  < 0.001), and insomnia ( r  = -0.402, p  < 0.001), respectively; effort-reward ratio and overcommitment were significantly positively correlated with insomnia ( r  = 0.379, p  < 0.001; r  = 0.466, p  < 0.001), respectively. In the model of perceived organizational support-psychological capital-effort-reward ratio-insomnia, the overall mediating effect was -0.080 (95%CI: -0.109 ~ -0.058), and the mediating effect of psychological capital was -0.050, accounting for 34.30% of the total effect; the mediating effect of effort-reward ratio was -0.024, accounting for 16.49% of the total effect; the chain mediating effect of psychological capital and effort-reward ratio was -0.007, accounting for 4.49% of the total effect. In the model of perceived organizational support-psychological capital-overcommitment-insomnia, the overall mediating effect was -0.085 (95%CI: -0.109 ~ -0.064), and the mediating effect of psychological capital was -0.042, accounting for 28.64% of the total effect; the mediating effect of overcommitment was -0.029, accounting for 19.81% of the total effect; the chain mediating effect of psychological capital and overcommitment was -0.015, accounting for 10.14% of the total effect., Conclusion: Perceived organizational support had direct negative influence on insomnia. Psychological capital and effort-reward ratio/overcommitment acted as chained mediating factor could partially relieve insomnia symptoms related to perceived organizational support. It is suggested to improve the level of organizational support and psychological capital of nurses, and reduce the effort-reward imbalance and overcommitment of nurses, so as to effectively decline and deal with nurses' insomnia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, He, Liu, Du, Wu, Lang and Du.)

Neuroligins (NLs), a family of postsynaptic cell-adhesion molecules, have been associated with autism spectrum disorder. We have reported that dysfunction of the medial prefrontal cortex (mPFC) leads to social deficits in an NL3 R451C knockin (KI) mouse model of autism. However, the underlying molecular mechanism remains unclear. Here, we find that N-methyl-D-aspartate receptor (NMDAR) function and parvalbumin-positive (PV+) interneuron number and expression are reduced in the mPFC of the KI mice. Selective knockdown of NMDAR subunit GluN1 in the mPFC PV+ interneuron decreases its intrinsic excitability. Restoring NMDAR function by its partial agonist D-cycloserine rescues the PV+ interneuron dysfunction and social deficits in the KI mice. Interestingly, early D-cycloserine administration at adolescence prevents adult KI mice from social deficits. Together, our results suggest that NMDAR hypofunction and the resultant PV+ interneuron dysfunction in the mPFC may constitute a central node in the pathogenesis of social deficits in the KI mice., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: This study aimed to evaluate the clinical outcome of Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) transplantation for recurrent pterygium with restrictive strabismus. (2) Methods: This retrospective study included 11 eyes in 11 patients diagnosed with recurrent pterygium with restrictive strabismus who received sandwich transplantation. The outcomes were measured by pterygium recurrence, best-corrected visual acuity, esotropia (prism diopters), and treatment complications. (3) Results: Eleven patients (six males, five females) had a mean age of 60.5 (range 36-80) years. The previously received pterygium excision surgery number was 1.8 ± 1.02 (range 1-4). The mean follow-up period was 19.9 ± 8.41 (range 12-36) months. All patients had a restriction of abduction in the previously operated eye, causing esotropia in the primary position. Pre-operative esotropia was 17.2 (range 10-30) prims diopter (PD). Five eyes (45.5%) had symblepharon before surgery. All patients were orthotropic until the last follow-up. Symblepharon was released in all eyes. Free ocular motility was present in all eyes. No donor site scar formation, scleral melt, or corneal ulcer was noted. (4) Conclusions: Sandwich transplantation for recurrent pterygium with restrictive strabismus is safe and effective.

Objective: Reflux esophagitis (RE) may be negatively correlated with Helicobacter pylori ( H. pylori ) infection, but the conclusion and relevant mechanism is still controversial. This study proposed to explore the correlation between RE and H. pylori infection based on natural population. Methods: From July 2013 to December 2014, 3 940 residents aged 40-69 years were recruited in Linqu County of Shandong Province and Hua County of Henan Province by the whole sampling method. All the subjects underwent gastroscopy, and gastric mucosa biopsy specimens were collected for pathological diagnosis and Warthin-Starry (WS) staining to identify H. pylori infection. Venous blood samples of some subjects were collected for H. pylori immunoglobulin G ( H. pylori -IgG) detection. Also, demographic and sociological data were collected. Chi-square test and logistic regression were used to analyze the correlation between RE and H. pylori infection. Results: A total of 359 cases of RE were detected. Excluding RE and other upper gastrointestinal organic diseases, 3 382 cases were considered as controls. Chi-square test showed that WS staining positive rate in RE group was significantly lower than that in control group ( P =0.023), but there was no significant difference in the positive rate of H. pylori -IgG between the two groups ( P =0.281). There were significant differences between RE group and control group in gender composition, age, body mass index (BMI), smoking, alcohol consumption, education level and mucosal active inflammation. Multivariate regression analysis showed that RE was negatively correlated with gastric mucosa active inflammation [ OR =0.754 (95% CI 0.600-0.949), P =0.016], and positively correlated with male [ OR =4.231 (95% CI 3.263-5.486), P <0.001], age ≥60 years, BMI≥24 kg/m 2 [ OR =1.540 (95% CI 1.220-1.945), P <0.001]. Compared to those aged 40-49 years and 50-59 years, the odds ratio ( OR ) of RE in these aged ≥60 years were 1.566 (95% CI 1.144-2.143, P =0.005) and 1.405 (95% CI 1.093-1.805, P =0.008). Conclusion: RE is more closely related to H. pylori present infection. Multivariate analysis showed that RE is negatively correlated with active inflammation of gastric mucosa caused by H. pylori infection, and positively correlated with male, overweight and aged ≥60 years.

Common bean ( Phaseolus vulgaris ) is an important food crop; however, its production is affected by salt stress. Salt stress can inhibit seed germination, promote senescence, and modify cell wall biosynthesis, assembly, and architecture. Melatonin, an indole heterocycle, has been demonstrated to greatly impact cell wall structure, composition, and regulation in plants under stress. However, the molecular basis for such assumptions is still unclear. In this study, a common bean variety, "Naihua" was treated with water (W), 70 mmol/L NaCl solution (S), and 100 μmol/L melatonin supplemented with salt solution (M+S) to determine the response of common bean to exogenous melatonin and explore regulatory mechanism of melatonin against salt stress. The results showed that exogenous melatonin treatment alleviated salt stress-induced growth inhibition of the common bean by increasing the length, surface area, volume, and diameter of common bean sprouts. Moreover, RNA sequencing (RNA-seq) and real-time quantitative PCR (qRT-PCR) indicated that the cell wall regulation pathway was involved in the salt stress tolerance of the common bean enhanced by melatonin. Screening of 120 germplasm resources revealed that melatonin treatment improved the salt tolerance of more than 65% of the common bean germplasm materials. Melatonin also up-regulated cell wall pathway genes by at least 46%. Furthermore, we analyzed the response of the common bean germplasm materials to melatonin treatment under salt stress using the key genes associated with the synthesis of the common bean cell wall as the molecular markers. The results showed that two pairs of markers were significantly associated with melatonin, and these could be used as candidate markers to predict whether common bean respond to exogenous melatonin and then enhance salt tolerance at the sprouting stage. This study shows that cell wall can respond to exogenous melatonin and enhance the salt tolerance of common bean. The makers identified in this study can be used to select common bean varieties that can respond to melatonin under stress. Overall, the study found that cell wall could response melatonin and enhance the salt tolerance and developed the makers for predicting varieties fit for melatonin under stress in common bean, which may be applied in the selection or development of common bean varieties with abiotic stress tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Qin, Wang, Zhang, Li, Yin, Yuan, Sun, Du, Du and Jia.)

Odorant-binding proteins (OBPs) play essential roles in lepidopteran insects' perception of host volatiles by binding and transporting hydrophobic ligands. The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a serious agricultural pest, with broad host range and cryptic feeding habits. However, few studies about YPM perceiving pheromones and host plant odorants have been reported. In this study, four OBP genes (CpunOBP8, CpunOBP9, CpunABP, and CpunGOBP2) were cloned from the antennae of YPM. The recombinant proteins were expressed and purified by prokaryotic expression system, with their binding affinities to 26 ligands being tested. Four CpunOBPs all had six conserved cysteine residues, which were typical structural characteristics of classical OBPs. The fluorescence competitive binding assay indicated that CpunOBP8 and CpunABP could not only exhibit high binding affinities to female sex pheromones, but also to host plant odorants. For example, CpunOBP8 bound strongly with cis-10-hexadecenal, hexadecanal, and so forth, whereas CpunABP bound with cis-10-hexadecenal, camphene, and 3-carene. Comparatively, CpunOBP9 and CpunGOBP2 could only bind with host plant odorants, with CpunOBP9 binding strongly to 3-methyl-1-butanol, hexyl acetate, and so forth, while CpunGOBP2 displaying the widest binding spectra and correlating with 3-carene, pentyl acetate, and so forth. The results indicated that on the one hand, each of the four CpunOBPs had its specific binding spectra when binding and transporting olfactory ligands; on the other hand, the same ligand might be bound to more than one CpunOBPs, which would provide information for the potential application of semiochemicals in controlling YPM., (© 2022 Wiley Periodicals LLC.)

Flavonoids are important secondary metabolites, active biomolecules in germinating beans, and have prominent applications in food and medicine due to their antioxidant effects. Rutin is a plant flavonoid with a wide biological activity range. In this study, flavonoid (rutin) accumulation and its related molecular mechanisms in germinating common bean ( Phaseolus vulgaris ) were observed at different time points (0-120 h) under salt stress (NaCl). The rutin content increased from germination onset until 96 h, after which a reducing trend was observed. Metabolome analysis showed that salt stress alters flavonoid content by regulating phenylpropanoid (ko00940) and flavonoid (ko00941) biosynthesis pathways, as well as their enzyme activities, including cinnamyl-alcohol dehydrogenase (CAD), peroxidase (POD), chalcone isomerase (CHI), and flavonol synthase (FLS). The RNA-seq and quantitative real-time PCR (qRT-PCR) analyses also showed that these two pathways were linked to changes in flavonoid content following salt treatment. These results reveal that salt stress effectively enhanced rutin content accumulation in germinating beans, hence it could be employed to enhance the functional quality of germinating common beans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zheng, Wang, Zhu, Zhou, Zhou, Xu, Sun, Zhong, Gu, Yin, Du and Du.)

Plant-associated microbes have been reported as important but overlooked drivers of plant-herbivorous insect interactions. Influence of plant-associated microbes on plant-insect interactions is diverse, including beneficial, detrimental, and neutral. Here, we determined the effects of three Penicillium fungi, including Penicillium citrinum, Penicillium sumatrense, and Penicillium digitatum, on the oviposition selection and behavior of the yellow peach moth (YPM), Conogethes punctiferalis (Guenée). Compared with fungi noninfected apples (NIA), mechanically damaged apples (MDA), and P. citrinum in potato dextrose agar medium (PC), the oviposition selection and four-arm olfactometer experiments both showed that mated YPM females preferred to P. citrinum-infected apples (PCA). For P. sumatrense or P. digitatum, we also found that mated YPM females preferred to P. sumatrense-infected apples (PSA) or P. digitatum-infected apples (PDA), respectively. Among three Penicillium fungi-infected apples, the selection rates including oviposition and olfactometer behavior of mated YPM females on PDA were both higher than those on PSA and PCA. Further analyses of host plant volatile organic compounds (VOCs) by GC-MS showed that the absolute contents of ethyl hexanoate and (Z, E)-α-farnesene in PCA, PSA, and PDA were all higher than those in NIA, and a total of 16 novel VOCs were detected in fungi-infected apples (PCA, PSA, and PDA), indicating that fungi infection changed the components and proportions of apple VOCs. Taken together, three Penicillium fungi play significant roles in mediating the host selection of YPMs via altering the emissions of VOCs. These findings will be beneficial for developing formulations for field trapping of YPMs in the future., (© 2022 Wiley Periodicals LLC.)

Spina bifida is the most common congenital defect of the central nervous system which can portend lifelong disability to those afflicted. While the complete underpinnings of this disease are yet to be fully understood, there have been great advances in the genetic and molecular underpinnings of this disease. Moreover, the treatment for spina bifida has made great advancements, from surgical closure of the defect after birth to the now state-of-the-art intrauterine repair. This review will touch upon the genetics, embryology, and pathophysiology and conclude with a discussion on current therapy, as well as the first FDA-approved clinical trial utilizing stem cells as treatment for spina bifida.

The nitrogen-nitrogen bond is a core feature of diverse functional groups like hydrazines, nitrosamines, diazos, and pyrazoles. Such functional groups are found in >300 known natural products. Such N-N bond-containing functional groups are also found in significant percentage of clinical drugs. Therefore, there is wide interest in synthetic and enzymatic methods to form nitrogen-nitrogen bonds. In this review, we summarize synthetic and biosynthetic approaches to diverse nitrogen-nitrogen-bond-containing functional groups, with a focus on biosynthetic pathways and enzymes.

Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p < 0.05). Through the CT manifestations and histopathological characteristics of PC under different immune function states, it was found that immune function has a significant impact on the CT manifestations and histopathological characteristics of patients with PC., (© 2022. The Author(s).)

Aim: To explore the relationships among self-efficacy, information literacy, social support and career success of clinical nurses and identify factors influencing clinical nurses' career success in northwestern China., Background: Understanding the influencing factors of career success is important for the professional development of nurses and the improvement of clinical nursing quality. Many influencing factors of career success have been identified, but there is no large-scale research on the relationships among self-efficacy, information literacy, social support and career success of clinical nurses based on Kaleidoscope Career Model. Studies examining the association of the four factors remain limited., Methods: A total of 3011 clinical nurses from 30 hospitals in northwestern China were selected in the cross-sectional survey, and the response rate was 94.71%. The clinical nurses completed the online self-report questionnaires including self-efficacy, information literacy, social support rating scale and career success scale. The data were analysed by SPSS23.0 statistical software using t test, analysis of variance, Pearson's correlation and multiple linear regression. Structural equation model (SEM) was used to analyse the influencing factors of career success using Mplus 8.3., Results: The career success of clinical nurses in northwestern China was at a medium level. The linear multivariate regression analysis showed that self-efficacy (β = .513), social support (β = .230), information support (β = .106), information consciousness (β = -.097), information knowledge (β = .067), information ethics (β = -.053), hospital grade (β = .118), marital status (β = -.071) and age (β = -.037) entered regression equation of clinical nurses' career success (all P < .05). SEM results showed that the career success was negatively correlated with demographic characteristics and positively correlated with social support and self-efficacy., Conclusion: Demographic characteristics, self-efficacy, social support and information literacy are the influencing factors of nurses' career success, which should be considered in the process of promoting nurses' career success., Implications for Nursing Management: Nursing managers need to acknowledge the significance of nurses' career success both for the realization of their own value and for the improvement of clinical nursing quality. They should encourage nurses to enhance self-efficacy and render more social support through incentive policies and foster nurses' information literacy through information technology training so as to improve their career success., (© 2021 The Authors. Journal of Nursing Management published by John Wiley & Sons Ltd.)

Objective: To explore the time trends of H. pylori infection and related drug use in patients with peptic ulcer bleeding (PUB) in recent ten years. Methods: PUB patients in Peking University Third Hospital from 2010 to 2019 were included. Time trends of H. pylori infection, related drugs (non-steroidal anti-inflammatory drugs, aspirin, antiplatelet drugs, anticoagulant drugs, glucocorticoids) use and non- H. pylori -non-drug ulcer in PUB patients were analyzed. Results: A total of 1 140 PUB patients were included from 2010 to 2019 (including 925 males and 215 females). The age M ( Q 1 , Q 3 )was 53.5 (33.0, 66.0) years, with 833 patients <65 years old. The positive rates of H. pylori were 79.3%, 75.7%, 73.1%, 71.6%, 77.0%, 70.4%, 69.7%, 63.1%, 51.4%, 50.9%, respectively, showing a decreasing trend (χ²=32.386, P <0.001), and the decreasing trends were significant in different ulcer location, age and gender subgroups(all P <0.05). The proportions of PUB patients using at least one of the above drugs were 23.1%, 28.6%, 34.0%, 39.5%, 33.8%, 35.9%, 28.7%, 39.8%, 40.9%, 41.8%, respectively, showing an increasing trend (χ²=6.857, P =0.009), and the proportions of patients with antiplatelet drugs and anticoagulant drugs history showed increasing trends. The proportions of non- H. pylori -non-drug patients were 12.3%, 22.1%, 14.6%, 13.2%, 7.7%, 13.0%, 16.9%, 18.7%, 22.6% and 20.9%, respectively, showing an increasing trend (χ²=4.808, P =0.028). Accordingly, the proportions of elderly (≥65 years old) patients (χ²=4.608, P =0.032) and large ulcer (≥2 cm) patients (χ²=8.173, P =0.004) showed increasing trends. Conclusion: In the last decade, the positive rate of H. pylori in PUB patients showed a decreasing trend, while the proportions of patients with antiplatelet drugs and anticoagulant drugs history and the proportion of non- H. pylori -non-drug patients showed increasing trends.

Deep learning techniques have the power to identify the degree of modification of high energy jets traversing deconfined QCD matter on a jet-by-jet basis. Such knowledge allows us to study jets based on their initial, rather than final, energy. We show how this new technique provides unique access to the genuine configuration profile of jets over the transverse plane of the nuclear collision, both with respect to their production point and their orientation. By effectively removing the selection biases induced by final-state interactions, one can analyze the potential azimuthal anisotropies of jet production associated to initial-state effects. Additionally, we demonstrate the capability of our new method to locate with precision the production point of a dijet pair in the nuclear overlap region, in what constitutes an important step forward toward the long term quest of using jets as tomographic probes of the quark-gluon plasma.

Molecules with a nitrogen-nitrogen (N-N) bond in their structures exhibit various biological activities and other unique properties. A few microbial proteins are recently emerging as dedicated N-N bond forming enzymes in natural product biosynthesis. However, the details of these biochemical processes remain largely unknown. Here, through in vitro biochemical characterization and computational studies, we report the molecular basis of hydrazine bond formation by a family of di-domain enzymes. These enzymes are widespread in bacteria and sometimes naturally exist as two standalone enzymes. We reveal that the methionyl-tRNA synthase-like domain/protein catalyzes ATP-dependent condensation of two amino acids substrates to form a highly unstable ester intermediate, which is subsequently captured by the zinc-binding cupin domain/protein and undergoes redox-neutral intramolecular rearrangement to give the N-N bond containing product. These results provide important mechanistic insights into enzymatic N-N bond formation and should facilitate future development of novel N-N forming biocatalyst., (© 2021. The Author(s).)

Background: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship., Methods: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies., Results: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73)., Conclusions: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection., (© 2021. The Author(s).)

The quality evaluation of hawthorn leaves in different geographical regions derived from the dried leaves of Crataegus pinnatifida Bge. Var. Major N.E.Br. or Crataegus pinnatifida Bge., a common blood-activating and stasis-eliminating traditional Chinese medicine, has hardly been reported. In this study, the chemical comparison of 40 batches of hawthorn leaf samples collected from Hebei, Liaoning, Shandong and Shanxi Provinces was performed using an ultra-high performance liquid chromatography with electrospray ionization-tandem mass spectrometry-based metabolic profile and pattern recognition analysis approach. A total of 233 compounds were determined. Among them, 40 compounds were selected as potential metabolites responsible for the differential clustering, and the differential metabolite-based evaluation model was applied to well distinguish the origin of seven batches of hawthorn leaves sold on the market. Further analysis of the KEGG pathway showed that five core metabolites containing flavonoids and lignins were mainly involved in flavonoid biosynthesis, flavone and flavonol biosynthesis, and stilbenoid, diarylheptanoid and gingerol biosynthesis. Taking the content of flavonoids, core markers, as the evaluation basis, it was found that the quality of hawthorn leaves in Hebei and Liaoning was better. The study provides a reference for the rational utilization of hawthorn leaves, and highlights that the metabolomics-driven analysis method is more suitable for the quality evaluation of traditional Chinese medicine.

Tinnitus can be described as the conscious perception of sound without external stimulation, and it is often accompanied by anxiety, depression, and insomnia. Current clinical treatments for tinnitus are ineffective. Although recent studies have indicated that the caudate-putamen nucleus may be a sensory gating area involved in noise elimination in tinnitus, the underlying mechanisms of this disorder are yet to be determined. To investigate the potential role of the caudate-putamen nucleus in experimentally induced tinnitus, we created a rat model of tinnitus induced by intraperitoneal administration of 350 mg/kg sodium salicylate. Our results revealed that the mean spontaneous firing rate of the caudate-putamen nucleus was increased by sodium salicylate treatment, while dopamine levels were decreased. In addition, electrical stimulation of the caudate-putamen nucleus markedly reduced the spontaneous firing rate of neurons in the primary auditory cortex. These findings suggest that the caudate-putamen nucleus plays a sensory gating role in sodium salicylate-induced tinnitus. This study was approved by the Institutional Animal Care and Use Committee of Peking University Health Science Center (approval No. A2010031) on December 6, 2017., Competing Interests: None

Crop plants grow, and then, they allocate resources to different structures, including seeds and fruits, which represent yield in most crops. We define the yield stability of a genotype as its ability to reduce the effects of temporal variation in resources and conditions on yield production, and we argue that yield stability can be understood in terms of two processes: (1) crop survival and growth (biomass production): the ability of the crop plants to survive and produce biomass under the range of conditions to which it is exposed and (2) the pattern of allocation of this biomass to yield across this range of conditions. Plant breeders and crop physiologists have focused on (1), but much less attention has been paid to (2). We hypothesize that (2) is primarily the result of reproductive allometry: the quantitative relationship between vegetative and reproductive biomass. Ecological theory and the allometric models we present predict a tradeoff between (a) the ability of a genotype to produce yield over a wide variety of conditions and (b) its ability to produce very high yields under optimal or near-optimal conditions. We reanalyze the data from two recent studies, and the results are consistent with this hypothesis. Yield stability in crops corresponds to bet-hedging in evolutionary ecological theory. It is the most appropriate strategy for smallholder farmers in developing countries, a group that comprises most of the farmers in the world. Researchers and crop breeders need to rethink their objectives if they want to develop optimal varieties for these farmers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Weiner, Du, Zhao and Li.)

Luzopeptins and related decadepsipeptides are bisintercalator nonribosomal peptides featuring rare acyl-substituted tetrahydropyridazine-3-carboxylic acid (Thp) subunits that are critical to their biological activities. Herein, we reconstitute the biosynthetic tailoring pathway in luzopeptin A biosynthesis through in vivo genetic and in vitro biochemical approaches. Significantly, we revealed a multitasking cytochrome P450 enzyme that catalyzes four consecutive oxidations including the highly unusual carbon-nitrogen bond desaturation, forming the hydrazone-bearing 4-OH-Thp residues. Moreover, we identified a membrane-bound acyltransferase that likely mediates the subsequent O-acetylation extracellularly, as a potential self-protective strategy for the producer strain. Further genome mining of novel decadepsipeptides and an associated P450 enzyme have provided mechanistic insights into the P450-mediated carbon-nitrogen bond desaturation. Our results not only reveal the molecular basis of pharmacophore formation in bisintercalator decadepsipeptides, but also expand the catalytic versatility of P450 family enzymes., (© 2021 Wiley-VCH GmbH.)

An efficient and straightforward palladium-catalyzed three-component cascade bisthiolation of terminal alkynes and arylhydrazines with sodium thiosulfate (Na 2 S 2 O 3 ) as the sulfur source for the assembly of functionalized ( Z )-1,2-bis(arylthio)alkene derivatives is described. Using 0.5 mol% IPr-Pd-Im-Cl 2 as the catalyst, a wide range of terminal alkynes and arylhydrazines are well tolerated, thus producing the desired products in good yields with good functional group tolerance and excellent regioselectivity. Moreover, this protocol could be readily scaled up, showing potential applications in organic synthesis and material science., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Microbial fermentation is currently still the major way to produce structural complicated clinical drugs. Yet, the low productivity and genetic instability of producing strains remain the bottlenecks in microbial pharmaceutical industry. Fidaxomicin is a microbial drug against the Clostridium difficile infection. Here, a genome-based combinatorial engineering strategy was established to improve both fidaxomicin production and the genetic stability of Actinoplanes deccanensis YP-1. Guided by genomic analysis, several genetic instability-associated elements were cumulatively deleted, generating a more genetically stable mutant. Further rational engineering approaches including elimination of a pigment pathway, duplication of the fidaxomicin gene cluster, overexpression of a positive regulator and optimization of the fermentation medium, led to an overall 27-folds improvement in fidaxomicin production. Taken together, the genome-based rational combinatorial engineering strategy was efficient to enhance the fidaxomicin production and ameliorate the genetic stability of YP-1, it can also be widely used in other industrial actinomycetes for strain improvement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to explore the incidence of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and the influence of hypoglycemia on the specific quality of life in T2DM patients., Methods: It was a comparative cross-sectional study consisting of 519 T2DM patients in Xi'an, China and patients were investigated by self-reported hypoglycemia and specific quality of life questionnaires from September 2019 to January 2020. Descriptive analysis, t-test, Chi-square test, hierarchical regression analysis and stepwise multiple regression analysis were applied to assess the influence of hypoglycemia on the specific quality of life., Results: The incidence of hypoglycemia in T2DM patients was 32.18%. The mean score of specific quality of life in diabetes without hypoglycemia was 57.33 ± 15.36 and was 61.56 ± 17.50 in those with hypoglycemia, which indicated that hypoglycemia had a serious impact on the quality of life of diabetics (t = - 5.172, p = 0.000). In the Univariate analysis of specific quality of life, age, education background, marital status, living status, duration of diabetes, monthly income per capita were independent and significant factors associated with specific quality of life of two groups of T2DM patients (p < 0.05). In the hierarchical regression analysis, the duration of the diabetes more than 11 years and the frequency of hypoglycemia more than 6 times in half a year entered the equation of specific quality of life of 519 diabetics respectively (p < 0.001). In multiple linear regression analysis, age, marital status and income all entered the regression equation of quality of life of the two groups (p < 0.05)., Conclusion: Hypoglycemia will have a serious impact on the quality of life of T2DM patients. In order to improve the living quality in diabetics, effective measurements should be taken to strengthen the management of blood glucose and to avoid hypoglycemia.