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Abstract The growing prevalence of mental health issues underscores the need for innovative screening methods. Large-scale, internet-based psychological screening has emerged as a vital tool to accurately determine morbidity rates and facilitate early diagnosis of mental disorders. However, conventional psychological screening methods often struggle with non-genuine responses and lack objective metrics. To bridge this gap, we have compiled a novel dataset derived from an expansive screening initiative at Xinxiang Medical University. The study, conducted from February 27 to March 17, 2021, yielded a dataset comprising responses from 24,292 students to four well-established psychological scales—PHQ-9, GAD-7, ISI, and PSS. A distinctive feature of this dataset is the inclusion of response time data, which captures the temporal dynamics of participants’ interactions with the scales, offering valuable insights into their response behaviour. The release of this dataset offers a substantial opportunity for researchers in the domains of psychology and public health to explore new insights into mental health, scale reliability, and the dynamics of psychological assessment.

Owing to the hexagonal close-packed (HCP) crystal structure inherent in Mg alloys, strong basal texture can readily be induced through the processes of rolling or extrusion. The anisotropy of the texture of Mg alloys impacts their stamping and forming capabilities, limiting their use in certain applications. Microalloying and shear deformation are currently the most common methods of weakening the texture of Mg alloys. Many shearing processes have been extensively studied, and given that they require complex equipment and make it difficult to achieve mass production, major attention has turned to studying the design of microalloys. Traditional trial-and-error approaches for developing micro-alloying confront many challenges, including longer test cycles and increasing expenses. The rapid advancement of big data and artificial intelligence opens up a new channel for the efficient advancement of metallic materials, specifically the application of machine learning to aid in the design of Mg alloys. ML modeling can be used to find correlations between features and attributes in data, allowing for the development and design of high-performance Mg alloys. The article provides an extensive overview of machine learning applications in Mg alloys. These include the discovery of high-performance alloys, the selection of coating designs, the design of Mg matrix composites, the prediction of second phases, the microstructure modification, optimization of rolling or extrusion parameters, and the prediction of mechanical and corrosion properties. In conclusion, challenges and prospects for the rational design of alloys with machine learning support were discussed.

To clarify the evolution of lamellar phases in the initial microstructure of the Mg-9Gd-0.8Al alloy during the extrusion process and the effect of lamellar phases on the dynamic recrystallization of the extruded Mg alloy, the solid solution treated Mg-9Gd-0.8Al (SS10) alloy, was extruded at different temperatures (380, 400, and 450 °C). With the extrusion temperature increasing, the average size of dynamically recrystallized (DRXed) grains and the second phases decreases firstly and then increases. However, the volume fraction of DRXed grains shows an opposite trend, while the amount of the second phases consistently decreases. The as-extruded SS10 alloy demonstrates superior mechanical properties when extruded at 400 °C, with a yield strength (YS) of 240 MPa, ultimate tensile strength (UTS) of 298 MPa, and elongation (EL) of 19.3%. The alloy achieves enhanced strength through grain boundary strengthening, dislocation strengthening, and Orowan strengthening. Moreover, the presence of DRXed grains with a weak texture plays a significant role in the improvement of the ductility of the alloy.

Purpose: This study aims to investigate patient characteristics with lens zonular ligament abnormalities in Acute Primary Angle Closure (APAC), identifying related risk factors, and evaluating the efficacy of Pilocarpine, a miotic agent. Design: Retrospective case-control study. Methods: Conducted as a retrospective case-control study at Hebei Provincial Eye Hospital from January 1, 2019, to December 31, 2021, the study included APAC cases undergoing ultrasound phacoemulsification with or without glaucoma surgery. Zonular ligament status was determined by intraoperative indicators such as lens equator visibility post-mydriasis and anterior capsule wrinkling during capsulorhexis. Patients were categorized into APAC and APAC with Lens Subluxation (APACLS) groups. Demographic details, Central Anterior Chamber Depth (ACD), Axial Length (AL), ACD difference between eyes (ACDD), Lens Thickness (LT), Lens Position (LP), and Relative Lens Position (RLP) were recorded and compared. Pilocarpine's impact on intraocular pressure reduction was assessed. Statistical analysis involved bilateral t-tests (for normally distributed data comparing both eyes in each group), non-parametric tests (for comparing two groups with non-normally distributed data), binary logistic regression, and Receiver Operating Characteristic (ROC) curve analysis for cutoff value determination related to zonular abnormalities. Results: The APAC and APACLS groups showed no significant difference in age of onset (70.11 ± 8.67 years vs. 70.11 ± 8.67 years, P = 0.159) or axial length of the eye (22.35 ± 0.64 mm vs. 22.36 ± 0.78 mm, P = 0.929). In the APACLS group, LT was greater (5.24 ± 0.37 mm vs. 5.01 ± 0.36 mm, P = 0.011), ACD was shallower (1.42 ± 0.24 mm vs. 1.69 ± 0.24 mm, P = 0.000), and ACDD was larger (0.38 ± 0.22 mm vs. 0.18 ± 0.18 mm, P = 0.000). The LP was lower (4.04 ± 0.32 vs. 4.20 ± 0.22, P = 0.013), and RLP was also lower (0.18 ± 0.02 vs. 0.19 ± 0.01, P = 0.015) in the APACLS group. A shallow ACD and a large ACDD were identified as risk factors associated with lens zonular abnormalities in the affected eyes (ACD OR value 63.97, P = 0.027; ACDD OR value 0.029, P = 0.027). Using ROC curve analysis, the cutoff value for ACDD was determined to be 0.375 mm, and for ACD, it was 1.6 mm. After pupil constriction with Pilocarpine eye drops, the proportion of patients whose intraocular pressure normalized was 75.36 % (52/69) in the APAC group and 71.43 % (25/35) in the APACLS group. Conclusion: ACD and ACDD in the affected eye are indicative of increased risk for APACLS. An ACD 0.375 mm should prompt consideration of zonular ligament abnormalities. Pilocarpine as a miotic treatment is safe and effective for such patients.

Abstract Background Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. Results Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. Conclusion In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

Abstract Background Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage is commonly observed in myopia with tilted optic disc. It presents with typical features on the fundus and follows a self-limiting course. However, due to its complex etiology, clinicians sometimes lack sufficient understanding of it which can easily lead to misdiagnosis or overtreatment. In this case report, we describe a rare case of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage in both eyes. Case presentation An 18-year-old female who has no past medical history experienced sudden black shadow blocking of her right eye in the right eye for the past 2 days after a 5-day history of COVID-19 infection. The best corrected visual acuity is 0.5 in the right eye and 0.6 in the left eye. Optical coherence tomography (OCT) showed tilted optic discs in both eyes, bulged nasal optic discs, and the presence of strong reflective material under the parafoveal retina of the optic discs. Fundus fluorescein angiography (FFA) showed subretinal fluorescence occlusion above and nasolateral to the optic disc in the right eye, with hypofluorescence below the optic disc; the subretinal below the optic disc was obscured by vitreous hemorrhage; hypofluorescence was seen in the optic disc region of the left eye.COVID-19 antigen was positive. The patient was in the early stage of the third COVID-19 infection when the disease occurred. We speculate that it may be related to it. After 5 months of conservative treatment, the patient’s hemorrhage disappeared in both eyes and her best corrected visual acuity returned to normal. Conclusions Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage usually occurs in myopia with tilted optic disc. In most patients, the cause of the bleeding is unknown, but it can gradually resolve under clinical observation or conservative treatment.

Abstract Purpose The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. Methods The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. Results The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. Conclusion Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.

Abstract Background With the development of single-cell technology, many cell traits can be measured. Furthermore, the multi-omics profiling technology could jointly measure two or more traits in a single cell simultaneously. In order to process the various data accumulated rapidly, computational methods for multimodal data integration are needed. Results Here, we present inClust+, a deep generative framework for the multi-omics. It’s built on previous inClust that is specific for transcriptome data, and augmented with two mask modules designed for multimodal data processing: an input-mask module in front of the encoder and an output-mask module behind the decoder. InClust+ was first used to integrate scRNA-seq and MERFISH data from similar cell populations, and to impute MERFISH data based on scRNA-seq data. Then, inClust+ was shown to have the capability to integrate the multimodal data (e.g. tri-modal data with gene expression, chromatin accessibility and protein abundance) with batch effect. Finally, inClust+ was used to integrate an unlabeled monomodal scRNA-seq dataset and two labeled multimodal CITE-seq datasets, transfer labels from CITE-seq datasets to scRNA-seq dataset, and generate the missing modality of protein abundance in monomodal scRNA-seq data. In the above examples, the performance of inClust+ is better than or comparable to the most recent tools in the corresponding task. Conclusions The inClust+ is a suitable framework for handling multimodal data. Meanwhile, the successful implementation of mask in inClust+ means that it can be applied to other deep learning methods with similar encoder-decoder architecture to broaden the application scope of these models.

To achieve a broad range of gradient strain from the rim to the center of a single specimen, the size of the high-throughput double-cone (DC) specimen was optimized using finite-element-model (FEM) simulation. As the deformation increased, the flow stress of the DC specimen quickly reached the maximum value, then gradually declined, and finally tended to be stable. The gradient microstructures corresponding to the gradient strains from the rim to the center of the DC specimen compressed at a certain temperature and strain rate were obtained by only one compression testing. As the equivalent strain increased, the degree of dynamic recrystallization (DRX) gradually rose from the rim to the center of the compressed DC specimen. However, when the equivalent strain and strain rate remained constant, the degree of DRX increased steadily with rising deformation temperature in the compressed DC specimens. Furthermore, during compression of the DC specimens at temperatures of 250 °C and 300 °C, the primary DRX mechanism was continuous dynamic recrystallization (CDRX). At temperatures of 350 °C and 400 °C, the DRX mechanism shifted, as both CDRX and discontinuous dynamic recrystallization (DDRX) were observed. This suggested that the DRX mechanism underwent a change as the deformation temperature increased.

This study presents a novel technology in the fabrication of AZ31 Mg alloy sheets using continuous shear extrusion (CSE) with multiple shear platforms at 340 °C. Compared with the conventional extrusion (CE), an asymmetric shear deformation was introduced so that the basal texture deflects towards to extrusion direction. Through finite element simulation, it was found that the differences in flow velocity and strain distributions along the thickness direction can be achieved by introducing the shear strain through CSE technology. Finer grains and more uniform microstructure were obtained in CSEed Mg samples compared to conventional extrusion. The average grain size decreased from 6.33 μm in CE samples to 3.94 μm in CSE samples, and 3.39 μm in CSE-II samples. The continuous asymmetric shear force also led to the basal plane inclining approximately 15° towards the extrusion direction, leading to a weakening of basal texture intensity. In terms of mechanical properties, the CSE Mg plates exhibited higher yield strength (YS), ultimate tensile strength (UTS), and fracture elongation (FE) along the extrusion direction. These improvements in mechanical performance can be attributed to enhanced work hardening ability, texture weakening, finer grains generation, and the dislocation strengthening induced by shear strain.

To investigate the role of pre-twins in Mg alloy sheets during warm planar deformation, the stretch forming is conducted at 200 °C. Results suggest the formability of the pre-twinned AZ31 Mg alloy sheet is enhanced to 11.30 mm. The mechanisms for the improved formability and the deformation behaviors during the planar stretch forming are systematically investigated based on the planar stress states. The Schmid factor for deformation mechanisms are calculated, the results reveal that planar stress states extremely affect the Schmid factor for {10-12} twinning. The detwinning is activated and the prismatic slip is enhanced in the pre-twinned sheet, especially under the planar extension stress state in the outer region. Consequently, the thickness-direction strain is accommodated better. The dynamic recrystallization (DRX) type is continuous DRX (CDRX) regardless of the planar stress state. However, the CDRX degree is greater under the planar extension stress state. Some twin lattices deviate from the perfect {10-12} twinning relation due to the planar compression stress state and the CDRX. The basal texture is weakened when the planar stress state tends to change the texture components.

Understanding selectivity-dependent molecular mechanism of inhibitors towards CDK2 over CDK6 is prominent for improving drug design towards the CDK family. Multiple short molecular dynamics (MD) simulations combined with MM-GBSA approach are adopted to investigate molecular mechanism on binding selectivity of inhibitors X64, X3A, and 4 AU to CDK2 and CDK6. The RMSF analysis and calculations of molecular surface areas indicate that local structural and global flexibility of CDK6 are stronger than that of CDK2. Based on dynamics cross-correlation maps (DCCMs), motion modes of CDK2 and CDK6 produce difference due to associations of X64, X3A, and 4 AU. The calculated binding free energies (BFEs) demonstrate that the compensation between binding enthalpy and entropy of X64, X34, and 4 AU is a key force driving selectivity of inhibitors towards CDK2 over CDK6. This work provides valuable information for designing highly selective inhibitors towards CDK2 and CDK6 and further promotes identification of efficient anticancer drugs in the future.

Abstract Introduction This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). Methods This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73–34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or

Creep aging forming (CAF) is a potential process used to manufacture large integral components of magnesium (Mg) alloys. The selected stress plays a crucial role in creep aging processes but the mechanism by which stress loading method affects creep aging of Mg alloys is still unclear. In this paper, the microstructural evolution of precipitated phases and precipitation-free zones (PFZ) at grain boundaries with different stress loading modes (unstressed, unidirectional tensile stress, and cyclic stress) at 250 °C were investigated along with changes in mechanical properties. The results showed that the addition of stress during aging effectively promoted the precipitation of precipitated phases, while unaffecting grain size. Unidirectional tensile stress caused directional growth of β′ phase ([101‾0]), as well as rotation of weave towards the basal plane texture, resulting in namely stress orientation effect. Solute atoms diffused in the direction of tensile stress while vacancies moved perpendicular to the direction of tensile stress, resulting in PFZ at grain boundaries (157.06 nm). By contrast, cyclic stresses led to the growth of β′ phase in three directions ([101‾0], [1‾100] and [01‾10]). The solute atoms and vacancies were uniformly distributed in the Mg matrix instead of directional diffusion, effectively reducing the width of PFZ (112.39 nm) at the grain boundary. These features significantly improved the mechanical properties of alloy specimens after cyclic stress creep aging when compared to unidirectional stress creep aging, with yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) enhanced from 171.6 MPa, 305.5 MPa, and 4.4% to 174.8 MPa, 326.3 MPa, and 6.9%, respectively.

To explore the effect of the precipitated phase particles and twins on the microstructure evolution and neutral layer evolution during bending, {10–12} tensile twins were introduced along the transverse direction (TD) on AZ80 Mg alloy sheets at room temperature. Then pre-compressed samples were aged to induce more precipitations. The reverse tensile tests were carried out at room temperature, and the three-point bending deformation was carried out at 100 °C. After aging treatment, precipitations increased. The results showed that twin crystals can promote precipitation formation. And the YS (yield strength) values of the pre-twinned aged samples were significantly larger than that before aging. During the bending process on the pre-compressed samples, the outside of the sample was dominated by the detwinning behaviors, while the inside region was dominated mainly by twinning. For pre-compressed bending samples, the k values were smaller than the initial bending sample. The tension and compression asymmetry in its inner and outer regions was weaker than that of the original bending sample. The existence of precipitations hindered the detwinning behaviors in outside the pre-twinning aged bending samples, and the twinning in inner region was restrained as well so that the inner and outer tension asymmetry decreased. The k values were smaller than that of the unaged samples, which was beneficial to weaken the bending springback of Mg alloy sheets.

Due to the hexagonal close-packed (HCP) crystal structure of Mg, the plasticity is poor at low temperatures. In order to solve this problem, the in-depth researches on various deformation modes of Mg are very necessary. However, there are many limitations to study these deformation modes in Mg polycrystals owing to the effect of grain boundaries, etc. It is more reasonable to conduct the researches in Mg single crystals, especially investigating the influence of crystal orientations, and the advantages of Mg single crystals are prominent particularly. On this basis, various investigations in Mg single crystals are carried out thoroughly in recent years, such as the critical resolved shear stress (CRSS) calculation, the slip and twinning modes activation determining, recrystallization behaviors and so on. In order to make clear the research advantages in Mg single crystals, a critical brief summary is conducted in this paper. Besides, various crystal plasticity finite element modeling (CPFEM) and electrochemical corrosion used in Mg single crystals are also reviewed. Finally, the current challenges and possible research directions are proposed.

Ti-Al-based alloys, particularly two-phase TiAl and Ti3Al alloys, have garnered significant attention as potential replacements for various high-temperature structural materials due to their exceptional properties, including low density, oxidation resistance, and high strength at elevated temperatures. Despite these advantages, experimental studies on the microstructure evolution of Ti-Al-based alloys under complex conditions remain challenging to observe and characterize. This review article examines the current research on molecular dynamics (MD) simulations of Ti-Al-based alloys, focusing on two-phase Ti-Al alloys, Ti-Al amorphous alloys, Ti-Al composite materials, and the welding and multi-layer/film applications of Ti-Al alloys. This review highlights the unique capabilities of MD simulations in predicting the behavior of Ti-Al-based alloys and addresses existing scientific challenges. Furthermore, this article discusses future research directions and development prospects in this field.

Fe-6.5 wt% Si high silicon steel alloy presents excellent soft magnetic performances, but a poor plasticity limits its industrial application seriously. In this work, a novel FeSiCrNi alloy with the chemical composition of Fe-6.5Si-2Cr-12Ni (wt%) is designed and subjected to thermomechanical processing including local canning compression at room temperature and annealing at elevated temperatures. It is observed that microstructures of FeSiCrNi specimens with a compression degree of 70 % are dominated by dislocation cells. The microstructural evolution is transformed from static recovery to static recrystallization when FeSiCrNi specimens are annealed from 400 to 700 °C. Grains with high strain energy are successively nucleated via the integration of subgrain boundaries at 600 °C and a pronounced growth of recrystallized grains occurs at 700 °C. In particular, microtextures of the FeSiCrNi alloy essentially consist of γ-fiber ({111}∥ND) and λ-fiber ({100}∥ND) textures during recovery and recrystallization. The intensity of λ-fiber texture is weakened with increasing annealing temperature, while the intensity of γ-fiber which is composed of {111} 〈112〉 and {111} 〈110〉 textures is strengthened. The intensity of {111} 〈112〉 texture within the recrystallized FeSiCrNi grains reaches the maximum value at 700 °C.

Abstract Background Stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is a rare type of retinoschisis with a spoke-like splitting that occurs in the outer plexus layer. We present a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a juvenile, in which two eyes show different development trends and macular retinoschisis could be associated with mechanical force in the Henle fibre layer. The removal of mechanical force can partially restore vision. Case presentation A 14-year-old girl with bilateral SNIFR was diagnosed and followed up with spectral-domain optical coherence tomography (SD-OCT). During the two follow-up visits, vitreous adhesion was released in the left eye, and visual acuity improved. Neuroepithelial detachment was aggravated in the right eye, and visual acuity decreased. Therefore, vitrectomy was performed on the right eye. After surgery, the patient’s retina was reattached, and her vision was partially restored. Conclusions We reported a juvenile with bilateral SNIFR. Each of her eyes showed different development trends, so we adopted different treatment methods for each eye. Vitrectomy was performed on the patient to address progressive vision loss, which improved the patient’s vision. It was further confirmed that the Henle layer of SNIFR patients was susceptible to posterior vitreous membrane adhesion.

Major Depressive Disorder (MDD) is a significant neurological condition associated with aberrations in brain functional networks. Traditional studies have predominantly analyzed these from a network topology perspective. However, given the brain’s dynamic and complex nature, exploring its mechanisms from a network control standpoint provides a fresh and insightful framework. This research investigates the integration of network controllability and machine learning to pinpoint essential biomarkers for MDD using functional magnetic resonance imaging (fMRI) data. By employing network controllability methods, we identify crucial brain regions that are instrumental in facilitating transitions between brain states. These regions demonstrate the brain’s ability to navigate various functional states, emphasizing the utility of network controllability metrics as potential biomarkers. Furthermore, these metrics elucidate the complex dynamics of MDD and support the development of precision medicine strategies that incorporate machine learning to improve the precision of diagnostics and the efficacy of treatments. This study underscores the value of merging machine learning with network neuroscience to craft personalized interventions that align with the unique pathological profiles of individuals, ultimately enhancing the management and treatment of MDD.

Abstract Background Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for lung cancer patients. Circular RNAs (circRNAs) have been revealed to participate in the chemoresistance in lung cancer. Hence, the role and mechanism of circ_0010235 in cisplatin resistance in lung cancer was investigated. Methods Expression levels of circ_0010235, microRNA (miR)‐379‐5p and E2F transcription factor 7 (E2F7) were analyzed using quantitative reverse transcription PCR (qRT‐PCR) and western blot. Cell DDP sensitivity, proliferation, apoptosis, invasion, and migration were detected by cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine (EDU) assay, flow cytometry and western blot, respectively. The binding interaction was verified using dual‐luciferase reporter assay. A murine xenograft model was established to investigate effects in vivo. Results Circ_0010235 was highly expressed in DDP‐resistant lung cancer tissues and cells. Knockdown of circ_0010235 elevated DDP sensitivity, constrained proliferation, invasion and migration as well as fostered apoptosis in DDP‐resistant lung cancer cells. Moreover, circ_0010235 silencing boosted DDP sensitivity and impeded tumor growth in lung cancer in vivo. Mechanistically, circ_0010235 acted as a sponge for miR‐379‐5p to elevate the expression of its target E2F7. Rescue experiments showed that miR‐379‐5p inhibition attenuated circ_0010235 knockdown‐evoked reduction on DDP resistance of DDP‐resistant cancer cells. In addition, miR‐379‐5p re‐expression elevated DDP sensitivity and suppressed the malignant phenotype of DDP‐resistant lung cancer cells through miR‐379‐5p. Conclusion Circ_0010235 knockdown reduced DDP resistance and tumor growth via miR‐379‐5p/ E2F7 axis in lung cancer, suggesting an effective therapeutic target for lung cancer patients.

The effects of Ca addition on the microstructure and mechanical properties of Mg–Zn–Sn–Mn alloys were investigated in this study. The Mg–6Zn–4Sn–1Mn–xCa (x = 0, 0.2, 0.5, 1 and 2 wt%) alloys consist of the α-Mg, Mg2Sn, Mg7Zn3, MgZn, α-Mn, CaMgSn, MgZn2, Mg2Ca and Ca2Mg6Zn3 phases. With increasing Ca content, the eutectic phase and grains were refined, and the morphologies of the CaMgSn phases changed from point-like to needle-like, rod-like and lath-like. At room temperature, small amounts of Ca can improve properties owing to refinement strengthening. The two-stage aged Mg–6Zn–4Sn–1Mn–0.2Ca alloy has the best comprehensive properties at room temperature, with an ultimate tensile strength (UTS), yield strength (YS) and elongation of 407 MPa, 392 MPa and 6.2%, respectively. When the Ca content increased, the number of CaMgSn phases increased, and the morphologies coarsened. Further, it was a brittle phase, resulting in the deterioration of alloy properties. At high temperatures, a small amount of Ca can improve the high-temperature plasticity. The elongations of the as-extruded Mg–6Zn–4Sn–1Mn–0.2Ca alloy were 76.9% (150 °C) and 133.8% (200 °C). A high Ca concentration can significantly improve the high-temperature strengths because of the good thermal stability of the CaMgSn phases, the best UTS and YS are 160 MPa and 136 MPa, respectively, in as-extruded Mg–6Zn–4Sn–1Mn–2Ca alloy at 150 °C.

AZ31 Mg alloy with heterogeneous bimodal grain structure (smaller grain size of 5–20 µm and coarser grain size of 100–200 µm) was subjected to accumulated extrusion bonding (AEB) at 250 ℃ combined with two-stage artificial cooling in this work, viz. local water cooling and artificial cooling. The microstructure developed consecutively as a result of discontinuous dynamic recrystallization (DDRX) for the AEBed samples. {10–12} tensile twinning also played an important role for the AEB with local water cooling at the initial extrusion stage in the container. Local water cooling could further reduce the DRXed grain size to ∼2.1 µm comparing that without water cooling. And the grain growth rate was reduced by artificial cooling out of extrusion die. Under the combination of two-stage cooling, the fine DRXed grains at sizing band were almost retained with average grain size of ∼2.3 µm after the sheet out of extrusion die, and the unDRXed grains with high residual dislocation density accumulation were also reserved. The tensile tests results indicated that a good strength-ductility balance with a high ultimate tensile strength (319 MPa vs. 412 MPa) and fracture elongation (19.9% vs. 30.3%) were obtained. The strength enhancement was mainly owing to the grain refinement and local residual plastic strain reserved by the artificial cooling. The excellent ductility originated from fine DRXed microstructure and ED-tilt double peak texture.

Abstract Electrochemical oxygen reduction reaction (ORR) is an attractive and alternative route for the on‐site production of hydrogen peroxide (H2O2). The electrochemical synthesis of H2O2 in neutral electrolyte is in early studying stage and promising in ocean‐energy application. Herein, N‐doped carbon materials (N‐Cx) with different N types are prepared through the pyrolysis of zeolitic imidazolate frameworks. The N‐Cx catalysts, especially N‐C800, exhibit an attracting 2e− ORR catalytic activity, corresponding to a high H2O2 selectivity (≈95%) and preferable stability in 0.5 m NaCl solution. Additionally, the N‐C800 possesses an attractive H2O2 production amount up to 631.2 mmol g−1 h−1 and high Faraday efficiency (79.8%) in H‐type cell. The remarkable 2e− ORR electrocatalytic performance of N‐Cx catalysts is associated with the N species and N content in the materials. Density functional theory calculations suggest carbon atoms adjacent to graphitic N are the main catalytic sites and exhibit a smaller activation energy, which are more responsible than those in pyridinic N and pyrrolic N doped carbon materials. Furthermore, the N‐C800 catalyst demonstrates an effective antibacterial performance for marine bacteria in simulated seawater. This work provides a new insight for electro‐generation of H2O2 in neutral electrolyte and triggers a great promise in ocean‐energy application.

The market value of tea is largely dependent on the tea species and cultivar. Therefore, it is important to develop efficient molecular markers covering the entire tea genome that can be used for the identification of tea varieties, marker-assisted breeding, and mapping important quantitative trait loci for beneficial traits. In this study, genome-wide molecular markers based on intron length polymorphism (ILP) were developed for tea trees. A total of 479, 1393, and 1342 tea ILP markers were identified using the PCR method in silico from the ‘Shuchazao’ scaffold genome, the chromosome-level genome of ‘Longjing 43’, and the ancient tea DASZ chromosome-level genome, respectively. A total of 230 tea ILP markers were used to amplify six tea tree species. Among these, 213 pairs of primers successfully characterize products in all six species, with 112 primer pairs exhibiting polymorphism. The polymorphism rate of primer pairs increased with the improvement in reference genome assembly quality level. The cross-species transferability analysis of 35 primer pairs of tea ILP markers showed an average amplification rate of 85.17% through 11 species in 6 families, with high transferability in Camellia reticulata and tobacco. We also used 40 pairs of tea ILP primers to evaluate the genetic diversity and population structure of C. tetracocca with 176 plants from Puan County, Guizhou Province, China. These genome-wide markers will be a valuable resource for genetic diversity analysis, marker-assisted breeding, and variety identification in tea, providing important information for the tea industry.

Background Schools play a crucial role in providing mental health services to children and adolescents. However, the vastness of the student population and mental health workforce shortage in China severely limit the capacity for adequate care access and delivery.Objective We propose a large, mixed longitudinal cohort study, ‘School-based Evaluation Advancing Response for Child Health (SEARCH)’, aimed at addressing the increasing demand from individuals seeking access to mental healthcare services.Methods SEARCH uses a digital platform and school-based protocol for comprehensive assessment of the mental well-being of Chinese students in grades 4–12 incorporating individual, caregiver and teacher input, including capture of facial and acoustic features and response times, as well as mental well-being assessments.Findings We completed first wave data collection from nearly 20 000 participants (students, caregivers and teachers) at 11 schools, grades 4–12, in 3 cities in Jiangsu province in Southeast China from September 2022 to February 2023. We intend to conduct follow-up assessments for grades 4 through 12 at the 11 school sites every 6 months for 5 years.Conclusions SEARCH will provide important insight into the developmental trajectory of mental well-being in Chinese children and adolescents. The study protocol does not simply focus on student self-report and incorporates caregiver and teacher viewpoints as well. It also collects objective indicators that may facilitate development of screening tools.Clinical implications We believe future study findings will guide the development and implementation of school-based mental healthcare initiatives to improve the well-being of children and adolescents.

Sansanmycins represent a family of uridyl peptide antibiotics with antimicrobial activity specifically against Mycobacterium tuberculosis (including drug-resistant M. tuberculosis) and Pseudomonas aeruginosa. They target translocase I (MraY) to inhibit bacterial cell wall assembly. Given the unique mechanism of action, sansanmycin has emerged as a potential lead compound for developing new anti-tuberculosis drugs, while the 5′-aminouridine moiety plays a crucial role in the pharmacophore of sansanmycin. For expanding the structural diversity of the 5′-aminouridine moiety of sansanmycin through biosynthetic methods, we firstly demonstrated that SsaM and SsaK are responsible for the biosynthesis of the 5′-aminouridine moiety of sansanmycin in vivo. Using the ssaK deletion mutant (SS/KKO), we efficiently obtained a series of new analogues with modified 5′-aminouridine moieties through mutational biosynthesis. Based on molecular networking analysis of MS/MS, twenty-two new analogues (SS-KK-1 to -13 and SS-KK-A to -I) were identified. Among them, four new analogues (SS-KK-1 to -3 and SS-KK-C) were purified and bioassayed. SS-KK-2 showed better antibacterial activity against E. coli ΔtolC than the parent compound sansanmycin A. SS-KK-3 showed the same anti-TB activity as sansanmycin A against M. tuberculosis H37Rv as well as clinically isolated, drug-sensitive and multidrug-resistant M. tuberculosis strains. Furthermore, SS-KK-3 exhibited significantly improved structural stability compared to sansanmycin A. The results suggested that mutasynthesis is an effective and practical strategy for expanding the structural diversity of 5′-aminouridine moiety in sansanmycin.

Progression to a severe condition remains a major risk factor for the COVID-19 mortality. Robust models that predict the onset of severe COVID-19 are urgently required to support sensitive decisions regarding patients and their treatments. In this study, we developed a multivariate survival model based on early-stage CT images and other physiological indicators and biomarkers using artificial-intelligence analysis to assess the risk of severe COVID-19 onset. We retrospectively enrolled 338 adult patients admitted to a hospital in China (severity rate, 31.9%; mortality rate, 0.9%). The physiological and pathological characteristics of the patients with severe and non-severe outcomes were compared. Age, body mass index, fever symptoms upon admission, coexisting hypertension, and diabetes were the risk factors for severe progression. Compared with the non-severe group, the severe group demonstrated abnormalities in biomarkers indicating organ function, inflammatory responses, blood oxygen, and coagulation function at an early stage. In addition, by integrating the intuitive CT images, the multivariable survival model showed significantly improved performance in predicting the onset of severe disease (mean time-dependent area under the curve = 0.880). Multivariate survival models based on early-stage CT images and other physiological indicators and biomarkers have shown high potential for predicting the onset of severe COVID-19.

Secondary phase changes after traditional aging and creep aging and corresponding effects on mechanical properties of Mg-9Gd-2Nd-0.5Zr alloys were studied. The results reveal that the presence of stress during the creep aging increases the concentration of dislocations in the alloy and provides abundant nucleus positions for β′ phase, promoting the precipitation rate of β′ phase in the alloy, which plays a critical role in shortening the peak aging time. In addition, the creep aging under unidirectional stress leads to the anisotropy of the solute atomic diffusion coefficient in the alloy, and the diffusion coefficient (Da/D) along the direction of tensile stress gradually decreases. At the same time, the tensile stress reduces the system energy and releases more energy to the β′ variants (C1) perpendicularly to the stress direction, resulting in preferentially-oriented precipitation and a decrease in alloy strength. There is a decrease in yield strength (YS) from 180.1 MPa to 166.8 MPa and ultimate tensile strength (UTS) from 321.3 MPa to 292.3 MPa after doing creep aging. Moreover, the presence of unidirectional stress during creep aging reduces the angle between the texture pole and basal plane texture, promoting the rotation of the grain orientation towards the basal plane in the alloy and increasing the alloy elongation to 9.5%.

Abstract Background With the rapid accumulation of scRNA-seq data, more and more automatic cell type identification methods have been developed, especially those based on deep learning. Although these methods have reached relatively high prediction accuracy, many issues still exist. One is the interpretability. The second is how to deal with the non-standard test samples that are not encountered in the training process. Results Here we introduce scCapsNet-mask, an updated version of scCapsNet. The scCapsNet-mask provides a reasonable solution to the issues of interpretability and non-standard test samples. Firstly, the scCapsNet-mask utilizes a mask to ease the task of model interpretation in the original scCapsNet. The results show that scCapsNet-mask could constrain the coupling coefficients, and make a one-to-one correspondence between the primary capsules and type capsules. Secondly, the scCapsNet-mask can process non-standard samples more reasonably. In one example, the scCapsNet-mask was trained on the committed cells, and then tested on less differentiated cells as the non-standard samples. It could not only estimate the lineage bias of less differentiated cells, but also distinguish the development stages more accurately than traditional machine learning models. Therefore, the pseudo-temporal order of cells for each lineage could be established. Following these pseudo-temporal order, lineage specific genes exhibit a gradual increase expression pattern and stem cell associated genes exhibit a gradual decrease expression pattern. In another example, the scCapsNet-mask was trained on scRNA-seq data, and then used to assign cell type in spatial transcriptomics that may contain non-standard sample of doublets. The results show that the scCapsNet-mask not only restored the spatial map but also identified several non-standard samples of doublet. Conclusions The scCapsNet-mask offers a suitable solution to the challenge of interpretability and non-standard test samples. By adding a mask, it has the advantages of automatic processing and easy interpretation compared with the original scCapsNet. In addition, the scCapsNet-mask could more accurately reflect the composition of non-standard test samples than traditional machine learning methods. Therefore, it can extend its applicability in functional analysis, such as fate bias prediction in less differentiated cells and cell type assignment in spatial transcriptomics.

To suppress the edge crack of the magnesium alloy sheet during the ordinary rolling process, a new rolling process named width-limited rolling was proposed in this paper. Width-limited rolling is a rolling method in which the width of the alloy sheet is limited by modifying the shape of the rollers, allowing a compressive stress field to form at the edge portion of the alloy sheet during rolling, resulting in the reduction of edge cracks. At present work, magnesium alloy sheets were separately subjected to ordinary rolling and width-limited rolling. The microstructure evolution and mechanical properties of the rolled sheets were investigated by EBSD, TEM, and XRD. The results exhibited that under the same rolling conditions, the sheet after ordinary rolling exhibited obvious edge cracks while no crack was found at the edge of the sheet after width-limited rolling. The edge crack suppressing effect was attributed to the reduction of the tensile stress along rolling direction during WLR, promoting the synchronous extension of the edge and center regions to suppress edge crack tendency. Microstructure observation showed that the compressive twins formed in the sheet after ordinary rolling usually exhibited as thin plates and cannot continue to fully develop due to the premature generation of the edge cracks. However, the compressive twins developed maturely in some of which double twins formed and various slip systems with different dislocation Burgers vectors occurred in the rolled sheet after WLR. More twin intersections and shear bands, providing more potential recrystallization nucleation sites, which are beneficial to weaken basal texture. With the cooperation of twinning and dislocation slip, the texture of the sheet after the width-limited rolling is weakened and the mechanical properties are improved.

China is one of the major mariculture countries for shellfish in the world and provides more than 70% of the total global shellfish production. However, there is limited knowledge of the potential driving factors of the ecosystem service value of mariculture shellfish in China. Understanding what factors and how they drive the ecosystem can provide reference for further improving the ecosystem service value of mariculture shellfish, which is both theoretically and practically important for promoting the development of marine fishery economy in China. In this study, data of six major mariculture shellfish species in nine coastal provinces of China from 2009 to 2020 were analyzed using a structural equation modeling approach to quantify the effects of resource distribution characteristics and market demand on the ecosystem service value of mariculture shellfish in China. The results indicated that both resource distribution characteristics and market demand are important driving factors of the ecosystem service value of mariculture shellfish in China. Specifically, from the perspective of path coefficient, market demand plays a more important role (0.58) than resource distribution characteristics (0.36) in influencing the ecosystem service value of mariculture shellfish in China. Therefore, the research results for shellfish marine culture can be summarized as: (1) to actively respond to changes in shellfish market demand, (2) to enhance development planning for coastal shellfish cultivation area, and (3) to strengthen systematic management of mariculture shellfish resources. Results of this study could provide theoretical support and serve as a basis for promoting sustainable development of shellfish culturing industry and fisheries economy in China.

In this study, AZ31 Mg alloy sheet was pre-twinned at room temperature along the transverse direction (TD) to introduce {10–12} tensile twins. The uniaxial tensile experiment was conducted at 200 °C to investigate the dynamic recrystallization, twinning behaviors and mechanical response. The strain paths tilted angles of 0°, 15°, 30°, 45°, 60°, 75° and 90° in respect to the rolling direction (RD) on the RD-TD plane were considered. Results revealed that the strain path has significant effects on the microstructural evolution and mechanical response at warm temperature. When the strain path tilts were 0°, 15°, 30°, 45° and 60° with the RD, continuous dynamic recrystallization (CDRX) was the main mechanism to coordinate strain. The detwinning dominated the microstructural evolution but retarded by CDRX for the pre-twinned sample with a strain path angle of 75°. Detwinning and CDRX played an important role on the microstructural evolution in the pre-twinned sample when the strain path was tilted 90°. Additionally, the effect of CDRX on {10–12} twinning and three types of {10–12} tensile twin behaviors were discussed. Both strengthening and weakening effects were observed in pre-twinned samples.

Abstract Background The long-term clinical status of coronavirus disease 2019 (COVID-19) in recovered patients remains largely unknown. This prospective cohort study evaluated clinical status of COVID-19 and explored the associated risk factors. Methods At the outpatient visit, patients underwent routine blood tests, physical examinations, pulmonary function tests, 6-min walk test, high-resolution computed tomography (CT) of the chest, and extrapulmonary organ function tests. Results 230 patients were analyzed. Half (52.7%) reported at least one symptom, most commonly fatigue (20.3%) and sleep difficulties (15.8%). Anxiety (8.2%), depression (11.3%), post-traumatic symptoms (10.3%), and sleep disorders (26.3%) were also reported. Diffusion impairments were found in 35.4% of the patients. Abnormal chest CT scans were present in 63.5% of the patients, mainly reticulation and ground-glass opacities. Further, a persistent decline in kidney function was observed after discharge. SARS-CoV-2-specific antibodies of IgA, IgG, and IgM were positive in 56.4%, 96.3%, and 15.2% of patients, respectively. Multivariable logistic regression showed that disease severity, age, and sex were closely related to patient recovery. Conclusions One year after hospital discharge, patients recovered from COVID-19 continued to experience both pulmonary and extrapulmonary dysfunction. While paying attention to pulmonary manifestations of COVID-19, follow-up studies on extrapulmonary manifestations should be strengthened.

Abstract Global changes such as seawater intrusion and freshwater resource salinization increase environmental stress imposed on the aquatic microbiome. A strong predictive understanding of the responses of the aquatic microbiome to environmental stress will help in coping with the “gray rhino” events in the environment, thereby contributing to an ecologically sustainable future. Considering that microbial ecological networks are tied to the stability of ecosystem functioning and that abundant and rare biospheres with different biogeographic patterns are important drivers of ecosystem functioning, the roles of abundant and rare biospheres in maintaining ecological networks need to be clarified. Here we showed that, with the increasing salinity stress induced by the freshwater‐to‐seawater transition, the microbial diversity reduced significantly and the taxonomic structure experienced a strong succession. The complexity and stability of microbial ecological networks were diminished by the increasing stress. The composition of the microorganisms supporting the networks underwent sharp turnovers during the freshwater‐to‐seawater transition, with the abundant biosphere behaving more robustly than the rare biosphere. Notably, the abundant biosphere played a much more important role than the rare biosphere in stabilizing ecological networks under low‐stress environments, but the difference between their relative importance narrowed significantly with the increasing stress, suggesting that the environmental stress weakened the “Matthew effect” in the microbial world. With in‐depth insights into the aquatic microbial ecology under stress, our findings highlight the importance of adjusting conservation strategies for the abundant and rare biospheres to maintain ecosystem functions and services in response to rising environmental stress.

Due to there being a lack of suitable approaches for evaluating the effectiveness of artificial reefs, two experiments were designed to examine the feasibility of acoustic telemetry, a rapidly developing method for tracking aquatic animals. The first experiment was conducted to understand the deployment procedures of an acoustic telemetry system and determine the appropriate deployment of receivers’ spacing, while the second experiment was conducted to quantify the site fidelity and habitat use of 11 reef fish in the Fangchenggang artificial reef area in the northern South China Sea, China. The results indicated that the logistic regression model was an effective way to balance the detection probability at different distances between the range test transmitter and receiver, with above 50% detection probability within 240 m and 80% detection probability within 110 m. The residency index, as a quantification of site fidelity, was 0.85 ± 0.24. The 100% minimum convex polygon, 95% kernel utilization distribution, and 50% kernel utilization distribution, which are the indicators of habitat use, were 34,522.94 ± 35,548.95, 1,467.52 ± 1,619.05, and 236.01 ± 294.59 m2, respectively. High site fidelity and the small spatial scale of habitat use for reef fish demonstrated that artificial reefs were an effective man-made structure to attract fish. Overall, this study supports the feasibility of the acoustic telemetry system, indicating that it provides a good approach for quantifying the associations between artificial reefs and fish.

In this paper, the homogenized Mg-9Gd-2Nd-1.6Zn-1Zr (wt%) alloys were subjected to various equal channel angular pressing (ECAP) passes (1, 2, 4 and 8) with Bc route at 400 °C. Then, the microstructure evolution and strengthening mechanisms of alloys were systematically investigated. The results show that the coarse deformed grains are completely consumed by the dynamic recrystallized (DRX) grains, the number of dynamic precipitates gradually increases, and the intensity of basal texture of the alloy is gradually weakened with increasing ECAP passes. After 8 passes ECAP, the grain size is dramatically refined from 50 μm (homogenized) to 2.1 μm (8p-ECAPed), which is mainly due to the DRX, particle-stimulated nucleation (PSN) induced by broken eutectic phase and hinder grain growth of dynamic precipitates. The excellent comprehensive mechanical properties are achieved by 4 passes, and the corresponding yield strength (YS) and ultimate tensile strength (UTS) as well as elongation (EL) are 321 MPa, 378 MPa and 14.4％, respectively. This can be mainly ascribed to the combined effect of broken eutectic phase, DRX grains, kinked long period-stacking order (LPSO) and dynamic precipitates.

In this study, accumulated extrusion bonding (AEB) process with application of artificial water cooling was successfully performed to fabricate fined-grains AZ31B Mg alloy sheets at 150 °C, 200 °C and 250 °C. The resultant microstructure and mechanical properties are systematically investigated. It reveals that the processing temperature has an important effect on the microstructural evolution during extrusion. During AEB process at 150 °C and 200 °C, {10–12} tensile twinning was activated at early stage of extrusion, and subsequently continuous dynamic recrystallization (CDRX) occurred and dominated the further deformation. However, for the sample extruded at 250 °C, hardly any twins can be observed, and new fined dynamic recrystallized grains were found along grain boundaries. Artificial cooling was utilized to reduce the rate of grain growth out of the extrusion die, resulting the grains significantly refined from 11 µm to 2.5 µm. Local high dislocation density region was also observed in the microstructure of sample processed at 150 °C in artificial cooling condition, and the degree decreased with the processing temperature increase. The results summarized from tensile tests indicated that due to the grain refinement the strength and ductility was significantly enhanced (YS of 186 MPa vs. 145 MPa, UTS of 391 MPa vs. 336 MPa and FE of 31.5% vs. 24.5% compared with the as-received sample). Subsequently, annealing treatment at different temperatures was applied to eliminate the high dislocation density. The sample annealed at 200 °C exhibited the best comprehensive mechanical property with YS of 179 MPa, UTS of 390 MPa and FE of 33.0%. As the annealing temperature increasing, the dislocation density was reduced by static recrystallization (SRX) and grain growth, leading to a decreased strength and ductility.

The ocean has considerable potential to function as a carbon sink, absorbing anthropogenic CO2 and buffering the effects of climate change. How the culture of shellfish can be used to increase the ocean carbon sink warrants evaluation. We analyze the production and carbon sink capacity of six important mariculture shellfish species (oyster, ark clam, mussel, scallop, clam, and razor clam) in nine coastal provinces of China from 1981–2020 using quality assessment and logarithmic mean Divisia index (LMDI) decomposition methods. Over this time period both cultured shellfish production and its contribution to the carbon sink generally increase, averaging approximately 600,000 t annually over the last four decades. Both the annual production and carbon sink capacity of China’s mariculture shellfish industry vary geographically. The total annual tonnage (scale) of cultured shellfish, and to a lesser extent, coastal shellfish species composition (structure) influence carbon sink capacity, and affect China’s plans to achieve “dual carbon goals.” Combining historical analysis and the LMDI method, we propose a scheme that optimally and more sustainably manages China’s culture of shellfish.

Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. Nine BGCs containing PKS and/or NRPS in Streptomyces globisporus C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter ermE*p in S. globisporus C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, three ortho-methyl phenyl alkenoic acids (compounds 1–3) were obtained. Gene disruption showed that compounds 1 and 2 were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes orf3 or echA in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the two adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.

Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is strongly associated with non-alcoholic steatohepatitis and advanced fibrosis; however, the underlying mechanisms remain largely unknown. In this study, we investigated the effect of PNPLA3-I148M on the activation of hepatic stellate cell line LX-2 and the progression of liver fibrosis. Immunofluorescence staining and enzyme-linked immunosorbent assay were used to detect lipid accumulation. The expression levels of fibrosis, cholesterol metabolism, and mitochondria-related markers were measured via real-time PCR or western blotting. Electron microscopy was applied to analyze the ultrastructure of the mitochondria. Mitochondrial respiration was measured by a Seahorse XFe96 analyzer. PNPLA3-I148M significantly promoted intracellular free cholesterol aggregation in LX-2 cells by decreasing cholesterol efflux protein (ABCG1) expression; it subsequently induced mitochondrial dysfunction characterized by attenuated ATP production and mitochondrial membrane potential, elevated ROS levels, caused mitochondrial structural damage, altered the oxygen consumption rate, and decreased the expression of mitochondrial-function-related proteins. Our results demonstrated for the first time that PNPLA3-I148M causes mitochondrial dysfunction of LX-2 cells through the accumulation of free cholesterol, thereby promoting the activation of LX-2 cells and the development of liver fibrosis.

Abstract Background Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. Methods This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. Results Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0–30, 31–60, 61–90, 91–120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. Conclusions Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

Abstract Background Bietti crystalline dystrophy (BCD) is an autosomal recessive genetic disorder that causes progressive vision loss. Here, 12 patients were followed up for 1–5 years with fundus fluorescein angiography (FFA) to observe BCD disease progression. Methods FFA images were collected for 12 patients with BCD who visited our clinic twice or more over a 5-year period. Peripheral venous blood was collected to identify the pathogenic gene related to the clinical phenotype. Results We observed two types in FFA images of patients with BCD. Type 1 showed retinal pigment epithelium (RPE) atrophy in the macular area, followed by choriocapillaris atrophy and the subsequent appearance of RPE atrophy appeared at the peripheral retina. Type 2 showed RPE atrophy at the posterior pole and peripheral retina, followed by choriocapillaris atrophy around the macula and along the superior and inferior vascular arcades and the nasal side of the optic disc. The posterior and peripheral lesions of both type 1 and type 2 BCD subsequently extended to the mid-periphery; finally, all the RPEs and choriocapillaris atrophied, exposing the choroid great vessels, but type 2 macular RPE atrophy could last longer. Conclusions The characterization of two different types of BCD development provides a better understanding of the phenotype and the progression of the disease for a precise prognosis and prediction of pathogenesis.

Introduction: Down syndrome (DS) is the leading cause of genetically defined intellectual disability and congenital birth defects worldwide. A large population of people diagnosed with DS globally is posing an enormous socioeconomic burden. However, the global burden and trends of DS have not been reported.Methods: Based on the data from the Global Burden of Disease database in 2019, we analyzed the incidence, prevalence, disability-adjusted life years (DALYs), and death of DS from 1990 to 2019 according to sex, age, regions, and social-demographic index (SDI). Then, age-standardized rates (ASRs) and estimated annual percentage change (EAPC) of these aforementioned indexes were calculated to evaluate the temporal trend of DS. Finally, the association of SDI with DS epidemiological parameters was assessed.Results: In the past 30 years, the incident cases, age-standardized incident rate (ASIR), and age-standardized prevalent rate (ASPR) of DS first decreased slightly and subsequently increased globally. The number of prevalent cases increased steadily, while the number and age-standardized rate (ASRs) of DALYs and deaths decreased gradually from 1990 to 2019. In the meantime, disease burdens were different across various SDI regions. The prevalent cases and ASPR for both sexes were increasing in all SDI regions except for the high-middle SDI region. At the national level, Brunei Darussalam, Ireland, and Haiti were the top three countries with the highest ASIR in 2019. Georgia was in the top three with the highest increase in ASRs of four parameters, while Serbia was consistently ranked in the top three with fastest declining. Furthermore, we found that ASIR and ASPR were positively correlated with SDI, yet the age-standardized DALYs and age-standardized death rate (ASDR) were negatively correlated with SDI.Conclusion: In the past 30 years, the burden and trends of DS were heterogeneous across different regions and countries with different sociodemographic characteristics. Great improvements had been achieved in reducing DALYs and deaths globally. However, the increased number and ASRs of incident and prevalent cases in some regions, especially in low SDI regions, were contributing to numerous challenges to public health. The findings may provide valuable information to the development or implementation of more effective measures.

Cyclic dimeric adenosine monophosphate (c-di-AMP) is a ubiquitous second messenger of bacteria involved in diverse physiological processes as well as host immune responses. MSMEG_2630 is a c-di-AMP phosphodiesterase (cnpB) of Mycobacterium smegmatis, which is homologous to Mycobacterium tuberculosis Rv2837c. In this study, cnpB-deleted (ΔcnpB), -complemented (ΔcnpB::C), and -overexpressed (ΔcnpB::O) strains of M. smegmatis were constructed to investigate the role of c-di-AMP in regulating mycobacterial physiology and immunogenicity. This study provides more precise evidence that elevated c-di-AMP level resulted in smaller colonies, shorter bacteria length, impaired growth, and inhibition of potassium transporter in M. smegmatis. This is the first study to report that elevated c-di-AMP level could inhibit biofilm formation and induce porphyrin accumulation in M. smegmatis by regulating associated gene expressions, which may have effects on drug resistance and virulence of mycobacterium. Moreover, the cnpB-deleted strain with an elevated c-di-AMP level could induce enhanced Th1 immune responses after M. tuberculosis infection. Further, the pathological changes and the bacteria burden in ΔcnpB group were comparable with the wild-type M. smegmatis group against M. tuberculosis venous infection in the mouse model. Our findings enhanced the understanding of the physiological role of c-di-AMP in mycobacterium, and M. smegmatis cnpB-deleted strain with elevated c-di-AMP level showed the potential for a vaccine against tuberculosis.

A multi-functional composite coating was fabricated on magnesium (Mg) AZ31 alloy through micro-arc oxidation (MAO) combined with self-assembly technology. Polyethyleneimine (PEI) as a medium was assembled on MAO coating based on the chemical bonding and electrostatic interactions. Adhered PEI successfully mediates the self-assembly of functional silver nanoparticles (Ag NPs) with a formation of Ag NPs/PEI/MAO (APM) composite coating. The morphology and microstructure of as-prepared APM coating were characterized by using of different technologies (e.g. scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy). Its corrosion behavior in simulated body fluid and the corresponding antibacterial performance against Staphylococcus aureus (S. aureus) were also investigated. The potentiodynamic polarization results showed that the corrosion current density of APM coated AZ31 decreased more than three orders of magnitude in comparison with that of uncoated AZ31, indicating an enhanced anticorrosive ability. Electrochemical impedance spectroscopy results further revealed that the improvement of corrosion resistance was attributed to a synergistic effect of Ag NPs/PEI and MAO. The hydrogen evolution tests confirmed that APM coating provided AZ31 an excellent corrosion protection during a relatively long term. And the antibacterial research showed that APM coated AZ31 had a great antibacterial activity. This study presents a promising approach to fabricate a multi-functional composite coating on Mg alloy, which improves the anticorrosive performance of the substrate and endows it an antibacterial activity to meet a better demand in the applications.

Abstract Background Norvancomycin has been widely used in clinic to treat against MRSA (Methicillin-resistant Staphylococcus aureus) and MRSE (Methicillin-resistant Staphylococcus epidermidis) infections in China. Amycolatopsis orientalis NCPC 2-48, a high yield strain derived from A. orientalis CPCC 200066, has been applied in industrial large-scale production of norvancomycin by North China Pharmaceutical Group. However, the potential high-yield and regulatory mechanism involved in norvancomycin biosynthetic pathway has not yet been addressed. Results Here we sequenced and compared the genomes and transcriptomes of A. orientalis CPCC 200066 and NCPC 2-48. These two genomes are extremely similar with an identity of more than 99.9%, and no duplication and structural variation was found in the norvancomycin biosynthetic gene cluster. Comparative transcriptomic analysis indicated that biosynthetic genes of norvancomycin, as well as some primary metabolite pathways for the biosynthetic precursors of norvancomycin were generally upregulated. AoStrR1 and AoLuxR1, two cluster-situated regulatory genes in norvancomycin cluster, were 23.3-fold and 5.8-fold upregulated in the high yield strain at 48 h, respectively. Over-expression of AoStrR1 and AoLuxR1 in CPCC 200066 resulted in an increase of norvancomycin production, indicating their positive roles in norvancomycin biosynthesis. Furthermore, AoStrR1 can regulate the production of norvancomycin by directly interacting with at least 8 promoters of norvancomycin biosynthetic genes or operons. Conclusion Our results suggested that the high yield of NCPC 2-48 can be ascribed to increased expression level of norvancomycin biosynthetic genes in its cluster as well as the genes responsible for the supply of its precursors. The norvancomycin biosynthetic genes are presumably regulated by AoStrR1 and AoLuxR1, of them AoStrR1 is possibly the ultimate pathway-specific regulator for the norvancomycin production. These results are helpful for further clarification of the holistic and pathway-specific regulatory mechanism of norvancomycin biosynthesis in the industrial production strain.

BRD9 and TAF1(2) have been regarded as significant targets of drug design for clinically treating acute myeloid leukemia, malignancies, and inflammatory diseases. In this study, multiple short molecular dynamics simulations combined with the molecular mechanics generalized Born surface area method were employed to investigate the binding selectivity of three ligands, 67B, 67C, and 69G, to BRD9/TAF1(2) with IC50 values of 230/59 nM, 1400/46 nM, and 160/410 nM, respectively. The computed binding free energies from the MM-GBSA method displayed good correlations with that provided by the experimental data. The results indicate that the enthalpic contributions played a critical factor in the selectivity recognition of inhibitors toward BRD9 and TAF1(2), indicating that 67B and 67C could more favorably bind to TAF1(2) than BRD9, while 69G had better selectivity toward BRD9 over TAF1(2). In addition, the residue-based free energy decomposition approach was adopted to calculate the inhibitor–residue interaction spectrum, and the results determined the gatekeeper (Y106 in BRD9 and Y1589 in TAF1(2)) and lipophilic shelf (G43, F44, and F45 in BRD9 and W1526, P1527, and F1528 in TAF1(2)), which could be identified as hotspots for designing efficient selective inhibitors toward BRD9 and TAF1(2). This work is also expected to provide significant theoretical guidance and insightful molecular mechanisms for the rational designs of efficient selective inhibitors targeting BRD9 and TAF1(2).