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Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

Abstract Background Sedentary behavior is prevalent among people with diabetes and is associated with unfavorable cardiometabolic health. However, there is limited evidence regarding the impact of replacing sedentary time (ST) with physical activity on mortality in people with prediabetes and diabetes. We prospectively examined the association between accelerometer-measured ST and mortality among people with prediabetes and diabetes after adjusting for demographic characteristics, lifestyle factors, and moderate- to vigorous-intensity PA (MVPA). We further determined the effect of replacing ST with equal time of different types of physical activities on all-cause mortality. Methods We included 1242 adults with prediabetes and 1037 with diabetes from the National Health and Nutrition Examination Survey. Restricted cubic splines were fitted to determine the dose–response association between ST and overall mortality. Isotemporal substitution modeling was used to explore the hazard ratio (HR) effects of ST replacement. Results During a median follow-up of 14.1 years, 424 adults with prediabetes and 493 with diabetes died. Compared with the lowest tertile of ST, the multivariable-adjusted HRs for all-cause mortality in the highest tertile were 1.76 (95% confidence interval [CI] 1.19, 2.60) for participants with prediabetes and 1.76 (1.17, 2.65) for those with diabetes. Additionally, a linear association between ST and all-cause mortality was observed in adults with prediabetes and diabetes, with HRs for each 60 min/day increment in ST of 1.19 (1.10, 1.30) and 1.25 (1.12, 1.40), respectively. Isotemporal substitution results indicated that individuals with prediabetes whose ST was replaced by 30 min of light-intensity physical activity (LPA) and MVPA had 9% and 40% lower all-cause mortality, respectively. In people with diabetes, replacing sedentary behavior with an equivalent time of LPA and MVPA was also associated with mortality risk reduction (HR 0.89; 95% CI 0.84, 0.95 for LPA; HR 0.73; 95% CI 0.49, 1.11 for MVPA). Conclusions Higher ST was associated in a dose–response manner with an increased risk of premature mortality among adults with prediabetes and diabetes. Statistically replacing ST with LPA was potentially beneficial for health in this high-risk population.

Abstract Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving “full coverage” treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Abstract Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter from Bordetella bronchiseptica at 3.05 Å resolution in an inward-facing, inhibited conformation. The transporter forms a homodimer, each protomer containing nine transmembrane helices and three metal ions. Two metal ions form a binuclear pore structure, and the third ion is located at an egress site facing the cytoplasm. The egress site is covered by a loop, and two histidine residues on the loop interact with the egress-site ion and regulate its release. Cell-based Zn2+ uptake and cell growth viability assays reveal a negative regulation of Zn2+ uptake through sensing intracellular Zn2+ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes.

Abstract Background Tumors possess incessant growth features, and expansion of their masses demands sufficient oxygen supply by red blood cells (RBCs). In adult mammals, the bone marrow (BM) is the main organ regulating hematopoiesis with dedicated manners. Other than BM, extramedullary hematopoiesis is discovered in various pathophysiological settings. However, whether tumors can contribute to hematopoiesis is completely unknown. Accumulating evidence shows that, in the tumor microenvironment (TME), perivascular localized cells retain progenitor cell properties and can differentiate into other cells. Here, we sought to better understand whether and how perivascular localized pericytes in tumors manipulate hematopoiesis. Methods To test if vascular cells can differentiate into RBCs, genome‐wide expression profiling was performed using mouse‐derived pericytes. Genetic tracing of perivascular localized cells employing NG2‐CreERT2:R26R‐tdTomato mouse strain was used to validate the findings in vivo. Fluorescence‐activated cell sorting (FACS), single‐cell sequencing, and colony formation assays were applied for biological studies. The production of erythroid differentiation‐specific cytokine, erythropoietin (EPO), in TME was checked using quantitative polymerase chain reaction (qPCR), enzyme‐linked immunosorbent assay (ELISA, magnetic‐activated cell sorting and immunohistochemistry. To investigate BM function in tumor erythropoiesis, BM transplantation mouse models were employed. Results Genome‐wide expression profiling showed that in response to platelet‐derived growth factor subunit B (PDGF‐B), neural/glial antigen 2 (NG2)+ perivascular localized cells exhibited hematopoietic stem and progenitor‐like features and underwent differentiation towards the erythroid lineage. PDGF‐B simultaneously targeted cancer‐associated fibroblasts to produce high levels of EPO, a crucial hormone that necessitates erythropoiesis. FACS analysis using genetic tracing of NG2+ cells in tumors defined the perivascular localized cell‐derived subpopulation of hematopoietic cells. Single‐cell sequencing and colony formation assays validated the fact that, upon PDGF‐B stimulation, NG2+ cells isolated from tumors acted as erythroblast progenitor cells, which were distinctive from the canonical BM hematopoietic stem cells. Conclusions Our data provide a new concept of hematopoiesis within tumor tissues and novel mechanistic insights into perivascular localized cell‐derived erythroid cells within TME. Targeting tumor hematopoiesis is a novel therapeutic concept for treating various cancers that may have profound impacts on cancer therapy.

Abstract The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2–5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Intelligent reflecting surface (IRS) is widely recognized as a promising technique to enhance the system performance, and thus is a hot research topic in future wireless communications. In this context, this paper proposes a robust BF scheme to improve the spectrum and energy harvesting efficiencies for the IRS-aided simultaneous wireless information and power transfer (SWIPT) in a cognitive radio network (CRN). Here, the base station (BS) utilizes spectrum assigned to the primary users (PUs) to simultaneously serve multiple energy receivers (ERs) and information receivers (IRs) through IRS-aided multicast technology. In particular, by assuming that only the imperfect channel state information (CSI) is available, we first formulate a constrained problem to maximize the minimal achievable rate of IRs, while satisfying the harvesting energy threshold of ERs, the quality-of-service requirement of IRs, the interference threshold of PUs and transmit power budget of BS. To address the nonconvex problem, we then adopt triangle inequality to deal with the channel uncertainty, and propose a low-complexity algorithm combining alternating direction method of multipliers (ADMM) with alternating optimization (AO) to jointly optimize the active and passive beamformers for the BS and IRS, respectively. Finally, our simulation results confirm the effectiveness of the proposed BF scheme and also provide useful insights into the importance of introducing IRS into the CRN with SWIPT.

Abstract Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors, including several that function to interfere with host ubiquitin signaling. Although the mechanism of action of many such effectors has been elucidated, how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined. In this study, we found that the SPI‐2 effector SseK3 inhibits SNARE pairing to promote the formation of a Salmonella‐induced filament by Arg‐GlcNAcylation of SNARE proteins, including SNAP25, VAMP8, and Syntaxin. Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the E3 ubiquitin ligase TRIM32, which catalyzes K48‐linked ubiquitination on SseK3 and targets its membrane‐associated portion for degradation. Hence, TRIM32 antagonizes SNAP25 Arg‐GlcNAcylation induced by SseK3 to restrict Salmonella‐induced filament biogenesis and Salmonella replication. Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factors.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds or even severe tissue damage. In this study, we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate (Cu-EGCG) nano-capsules. The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It could also promote the proliferation and migration of L929 fibroblasts. In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect. Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group. The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.

Abstract Congenital heart disease (CHD) is the most common type of birth defect and the main noninfectious cause of death during the neonatal stage. The non-POU domain containing, octamer-binding gene, NONO, performs a variety of roles involved in DNA repair, RNA synthesis, transcriptional and post-transcriptional regulation. Currently, hemizygous loss-of-function mutation of NONO have been described as the genetic origin of CHD. However, essential effects of NONO during cardiac development have not been fully elucidated. In this study, we aim to understand role of Nono in cardiomyocytes during development by utilizing the CRISPR/Cas9 gene editing system to deplete Nono in the rat cardiomyocytes H9c2. Functional comparison of H9c2 control and knockout cells showed that Nono deficiency suppressed cell proliferation and adhesion. Furthermore, Nono depletion significantly affected the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in H9c2 overall metabolic deficits. Mechanistically we demonstrated that the Nono knockout impeded the cardiomyocyte function by attenuating phosphatidyl inositol 3 kinase-serine/threonine kinase (Pi3k/Akt) signaling via the assay for transposase-accessible chromatin using sequencing in combination with RNA sequencing. From these results we propose a novel molecular mechanism of Nono to influence cardiomyocytes differentiation and proliferation during the development of embryonic heart. We conclude that NONO may represent an emerging possible biomarkers and targets for the diagnosis and treatment of human cardiac development defects.

Abstract Cell fate decision involves rewiring of the genome, but remains poorly understood at the chromatin level. Here, we report that chromatin remodeling complex NuRD participates in closing open chromatin in the early phase of somatic reprogramming. Sall4, Jdp2, Glis1 and Esrrb can reprogram MEFs to iPSCs efficiently, but only Sall4 is indispensable capable of recruiting endogenous components of NuRD. Yet knocking down NuRD components only reduces reprogramming modestly, in contrast to disrupting the known Sall4-NuRD interaction by mutating or deleting the NuRD interacting motif at its N-terminus that renders Sall4 inept to reprogram. Remarkably, these defects can be partially rescured by grafting NuRD interacting motif onto Jdp2. Further analysis of chromatin accessibility dynamics demonstrates that the Sall4-NuRD axis plays a critical role in closing the open chromatin in the early phase of reprogramming. Among the chromatin loci closed by Sall4-NuRD encode genes resistant to reprogramming. These results identify a previously unrecognized role of NuRD in reprogramming, and may further illuminate chromatin closing as a critical step in cell fate control.

Abstract Cryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer the knowledge to restore signals in cryo-ET. Test results on the simulated and real cryo-ET datasets show that REST performs well in denoising and compensating the missing wedge information. The application in dynamic nucleosomes, presenting either in the form of individual particles or in the context of cryo-FIB nuclei section, indicates that REST has the capability to reveal different conformations of target macromolecules without subtomogram averaging. Moreover, REST noticeably improves the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.

Microbial scale-up cultivation is the first step to bioremediating cadmium (Cd)-contaminated soils at the industrial scale. However, the changes in the microbial community as the bioreactor volume expands and their associations with soil Cd removal remain unclear. Herein, a six-stage scale-up cultivation process of mixotrophic acidophiles was conducted, scaling from 0.1 L to 10 m3, to remediate Cd-contaminated soils. The findings showed that bioreactor expansion led to a delay in sulfur and glucose oxidations, resulting in a reduced decline in solution pH and cell density. There were minimal differences observed in bacterial alpha-diversity and community structure as the bioreactor volume increased, except for the 10 m3 scale. However, bioreactor expansion decreased fungal alpha-diversity, changed the community structure, and simplified fungal community compositions. At the family level, Acidithiobacillaceae and Debaryomycetaceae dominated the bacterial and fungal communities throughout the scale-up process, respectively. Correlation analysis indicated that the indirect effect of mixotrophic acidophiles played a significant role in soil Cd removal. Bacterial community shifts, driven by changes in bioreactor volume, decreased the pH value through sulfur oxidation, thereby indirectly enhancing Cd removal efficiency. This study will contribute to the potential industrial application of mixotrophic acidophiles in bioremediating Cd-contaminated soils.

(Cu,C)Ba2Ca3Cu4Oy is a nontoxic cuprate superconducting material with a superconducting transition temperature of about 116 K. Recently, it was found that bulk samples of this material synthesized under high pressure hold the highest irreversibility line among all the superconductors, which is very promising for its application in the liquid nitrogen temperature field. In this work, high-temperature (Cu,C)Ba2Ca3Cu4Oy superconducting films with large irreversible fields were prepared on SrLaAlO4(00l) substrates by pulsed laser deposition. The substrate temperature during deposition proved to be the most important parameter determining the morphology and critical temperature of the superconductors, with 680 °C considered to be the optimum temperature. X-ray diffraction (XRD) results showed that the (Cu,C)Ba2Ca3Cu4Oy films prepared under optimal conditions exhibited epitaxial growth with the a-axis perpendicular to the film surface and the b- and c-axes parallel to the substrate, with no evidence of any other orientation. In addition, resistivity measurements showed that the onset transition temperature (Tconset) was approximately 116 K, the zero-resistance critical temperature (Tc0) was around 53 K, and the irreversible field (Hirr) was about 9 T at 37 K for (Cu,C)Ba2Ca3Cu4Oy films under optimal temperature. This is the first example of the successful growth of superconducting (Cu,C)Ba2Ca3Cu4Oy films on SrLaAlO4(00l) substrates. This will facilitate high-performance applications of (Cu,C)Ba2Ca3Cu4Oy superconducting materials in the liquid nitrogen temperature field.

The second brightest gamma-ray burst, GRB 230307A (with a duration T _90 ∼ 40 s), exhibited characteristics indicative of a magnetar engine during the prompt emission phase. Notably, a suspected kilonova was identified in its follow-up optical and infrared observations. Here we propose that the origin of GRB 230307A is a neutron star–white dwarf (NS–WD) merger as this could naturally explain the long duration and the large physical offset from the center of its host galaxy. In the framework of such an NS–WD merger event, the late-time kilonova-like emission is very likely to be powered by the spin-down of the magnetar and the radioactive decay of ^56 Ni, rather than by the decay of r -process elements as these heavy elements may not easily be synthesized in an NS-WD merger. It is demonstrated that the above scenario can be supported by our fit to the late-time observational data, where a mass of ∼10 ^−3 M _⊙ ^56 Ni is involved in the ejecta of a mass of ∼0.1 M _⊙ . Particularly, the magnetar parameters required by the fit are consistent with those derived from the early X-ray observation.

Abstract Background Asthma associated with obesity is a chronic disease characterized by earlier airway remodeling, severe wheezing, and increased insensitivity to hormone therapy. Reticuline, a bioactive compound of Magnoliae Flos, exerts anti‐inflammatory activity and can inhibit neutrophil recruitment. Thus, this study investigated the role of reticuline in obesity‐related asthma. Methods The BALB/c mice fed a low‐fat diet (LFD) and high‐fat diet (HFD) were intranasally challenged with house dust mites (HDMs) or ovalbumin (OVA). Reticuline (0.25 mg/kg) was administrated into mice by intragastrical gavage. Airway hyper‐responsiveness was examined after the final challenge. Body weight was measured, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The number of inflammatory cells in BALF was estimated. Histological changes were assessed by performing hematoxylin–eosin staining, and production of proinflammatory cytokines and IgE was examined by ELISA kits. Related pathways were studied with western blotting. Results Reticuline suppressed airway resistance and inflammatory infiltration in lung tissue and reduced inflammatory cell recruitment in BALF in obesity mice with asthma. Additionally, the levels of IL‐17A, IL‐1β, IL‐5, macrophage inflammatory protein 2, and regulated on activation, normal T cell expressed and secreted in the lung were reduced by reticuline. Mechanistically, reticuline inactivated the JAK2/STAT3/SOCS3 and p38 MAPK/NF‐κB signaling pathways in obesity‐related asthma. Conclusion Reticuline alleviates airway inflammation in obesity‐related asthma by inactivating the JAK2/STAT3/SOCS3 and p38 MAPK/NF‐κB signaling pathways.

The deficiency of clinically specific biomarkers has made it difficult to achieve an accurate diagnosis of temporomandibular joint osteoarthritis (TMJ-OA) and the insufficient comprehension of the pathogenesis of the pathogenesis of TMJ-OA has posed challenges in advancing therapeutic measures. The combined use of metabolomics and transcriptomics technologies presents a highly effective method for identifying vital metabolic pathways and key genes in TMJ-OA patients. In this study, an analysis of synovial fluid untargeted metabolomics of 6 TMJ-OA groups and 6 temporomandibular joint reducible anterior disc displacement (TMJ-DD) groups was conducted using liquid and gas chromatography mass spectrometry (LC/GC-MS). The differential metabolites (DMs) between TMJ-OA and TMJ-DD groups were analyzed through multivariate analysis. Meanwhile, a transcriptomic dataset (GSE205389) was obtained from the GEO database to analyze the differential metabolism-related genes (DE-MTGs) between TMJ-OA and TMJ-DD groups. Finally, an integrated analysis of DMs and DE-MTGs was carried out to investigate the molecular mechanisms associated with TMJ-OA. The analysis revealed significant differences in the levels of 46 DMs between TMJ-OA and TMJ-DD groups, of which 3 metabolites (L-carnitine, taurine, and adenosine) were identified as potential biomarkers for TMJ-OA. Collectively, differential expression analysis identified 20 DE-MTGs. Furthermore, the integration of metabolomics and transcriptomics analysis revealed that the tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, ferroptosis were significantly enriched. This study provides valuable insights into the metabolic abnormalities and associated pathogenic mechanisms, improving our understanding of TMJOA etiopathogenesis and facilitating potential target screening for therapeutic intervention.

Wolf–Rayet stars in close binary systems can be tidally spun up by their companions, potentially leaving behind fast-spinning, highly magnetized neutron stars, known as “magnetars,” after core collapse. These newborn magnetars can transfer rotational energy into heating and accelerating the ejecta, producing hydrogen-poor superluminous supernovae (SLSNe). In this Letter, we propose that the magnetar wind of the newborn magnetar could significantly evaporate its companion star, typically a main-sequence or helium star, if the binary system is not disrupted by the abrupt mass loss and supernova (SN) kick. The subsequent heating and acceleration of the evaporated star material along with the SN ejecta by the magnetar wind can produce a postpeak bump in the SLSN lightcurve. Our model can reproduce the primary peaks and postpeak bumps of four example observed multiband SLSN lightcurves, revealing that the mass of the evaporated material could be ∼0.4–0.6 M _⊙ if the material is hydrogen-rich. We propose that the magnetar could induce strongly enhanced evaporation from its companion star near the pericenter if the orbit of the post-SN binary is highly eccentric, ultimately generating multiple postpeak bumps in the SLSN lightcurves. This “magnetar–star binary engine” model may offer a possible explanation for the evolution of polarization, along with the origin and velocity broadening of late-time hydrogen or helium broad spectral features observed in some bumpy SLSNe. The diversity in the lightcurves and spectra of SLSNe may be attributed to the wide variety of companion stars and post-SN binary systems.

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients’ quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.

The hygiene hypothesis proposes that decreased exposure to infectious agents in developed countries may contribute to the development of allergic and autoimmune diseases. Trichinella spiralis, a parasitic roundworm, causes trichinellosis, also known as trichinosis, in humans. T. spiralis had many hosts, and almost any mammal could become infected. Adult worms lived in the small intestine, while the larvae lived in muscle cells of the same mammal. T. spiralis was a significant public health threat because it could cause severe illness and even death in humans who eat undercooked or raw meat containing the parasite. The complex interactions between gastrointestinal helminths, gut microbiota, and the host immune system present a challenge for researchers. Two groups of mice were infected with T. spiralis vs uninfected control, and the experiment was conducted over 60 days. The 16S rRNA gene sequences and untargeted LC/MS-based metabolomics of fecal and serum samples, respectively, from different stages of development of the Trichinella spiralis-mouse model, were examined in this study. Gut microbiota alterations and metabolic activity accompanied by parasite-induced immunomodulation were detected. The inflammation parameters of the duodenum (villus/crypt ratio, goblet cell number and size, and histological score) were involved in active inflammation and oxidative metabolite profiles. These profiles included increased biosynthesis of phenylalanine, tyrosine, and tryptophan while decreasing cholesterol metabolism and primary and secondary bile acid biosynthesis. These disrupted metabolisms adapted to infection stress during the enteral and parenteral phases and then return to homeostasis during the encapsulated phase. There was a shift from an abundance of Bacteroides in the parenteral phase to an abundance of probiotic Lactobacillus and Treg-associated-Clostridia in the encapsulated phase. Th2 immune response (IL-4/IL-5/IL-13), lamina propria Treg, and immune hyporesponsiveness metabolic pathways (decreased tropane, piperidine and pyridine alkaloid biosynthesis and biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid) were all altered. These findings enhanced our understanding of gut microbiota and metabolic profiles of Trichinella -infected mice, which could be a driving force in parasite-shaping immune system maintenance.

ABSTRACTObjectives Autologous hematopoietic stem cell transplantation (ASCT) is a crucial method used in patients with multiple myeloma (MM). This study aims to evaluate the role of ASCT in immunoglobulin (Ig) reconstitution and long-term outcomes in patients aged ≥ 60 years.Methods From March 2008 to May 2019, 93 patients aged ≥ 60 years who were diagnosed with MM and underwent ASCT were retrospectively analyzed. All patients underwent follow-ups and the deadline for follow-up was October 31, 2022. The Ig levels were measured using the immune turbidimetry method at 3, 6, and 12 months after transplantation. Patients who died or experienced relapse were excluded from the analysis. The prognostic value of Ig levels was estimated using the Kaplan-Meier survival curve and Cox regression method.Results No patients died, and all patients with complications showed improvements after treatment. Patients in the Ig reconstitution group had a lower international staging system (ISS) stage, whereas those in the immunoparesis group had a higher ISS stage. The median duration of follow-up was 36 (range, 13–120) months. The Ig reconstitution within 12 months indicated a longer overall survival and progression-free survival outcomes. The detection of Ig levels was an independent indicator for the prognosis of MM.Discussion and conclusion The Ig reconstitution within 12 months of ASCT could predict the overall outcomes of patients with MM aged ≥ 60 years.

Methanogenic archaea play an important role in the global carbon cycle and may serve as host organisms for the biotechnological production of fuels and chemicals from CO2 and other one-carbon substrates. Methanosarcina acetivorans is extensively studied as a model methanogen due to its large genome, versatile substrate range, and available genetic tools. Genome editing in M. acetivorans via CRISPR/Cas9 has also been demonstrated. Here, we describe a user-friendly CRISPR/Cas12a toolbox that recognizes T-rich (5′-TTTV) PAM sequences. The toolbox can manage deletions of 3,500 bp (i.e., knocking out the entire frhADGB operon) and heterologous gene insertions with positive rates of over 80%. Cas12a-mediated multiplex genome editing was used to edit two separate sites on the chromosome in one round of editing. Double deletions of 100 bp were achieved, with 8/8 of transformants being edited correctly. Simultaneous deletion of 100 bp at one site and replacement of 100 bp with the 2,400 bp uidA expression cassette at a separate site yielded 5/6 correctly edited transformants. Our CRISPR/Cas12a toolbox enables reliable genome editing, and it can be used in parallel with the previously reported Cas9-based system for the genetic engineering of the Methanosarcina species.

Introduction Acute pancreatitis (AP) is characterised by inflammation of the exocrine pancreas, which potentially leads to local complications and organ failure resulting in significant morbidity and mortality. A long-term follow-up by an experienced team is needed. Currently, a variety of outcome measures are used in clinical trials for patients with AP. However, due to heterogeneous and selective outcome reporting across trials of interventions, it is hard to combine or compare the trial results compromising systematic evaluations of effectiveness and safety. A core outcome set is demanded to standardise reporting for the management of AP in clinical trials, so as to conduct systematic reviews and to improve the quality of the existing evidence base on the management of AP. We designed a study to establish a core outcome set (COS) on what indicators should be measured and reported in clinical trials of patients with AP (COS-AP).Methods and analysis This study protocol outlines the following five phases: Phase I will be a systematic review of randomised control trials and semistructured interviews with patients to initially establish a preliminary list of potential outcomes. Phase II will be the recruitment of key stakeholders’ groups comprising experts in pancreatic disease, clinical researchers, methodologists, journal editors and patients. Phase III will be two rounds of the Delphi surveys with key stakeholder groups. Phase IV will be a consensus on the outcomes that should be included in a final COS-AP. Phase V will be dissemination of COS-AP.Ethics and dissemination Ethical approval for this study was obtained from the Biomedical Research Ethics Committee (BREC) of West China Hospital of Sichuan University (2020 No.691). The findings will be disseminated in peer-reviewed journals and meetings.Trial registration This study was registered with Core Outcome Measures in Effectiveness Trials (COMET) database as study 2573.

Rational chemical fertilizer application, especially combined with manure or straw amendment, serves as a key strategy for facilitating soil organic carbon (SOC) sequestration and soil fertility improvement. However, the effects of fertilization managements on the SOC priming induced by straw return remains unclear. Here, a microcosm was conducted to clarify the mechanisms of 13C-labeled maize straw addition effects on priming effect (PE) in two 29-year fertilized soils (Urumqi, UQ; Gongzhuling, GZL) subjected to four fertilization regimes (no fertilizer, CK; chemical fertilizers, NPK; combined application of NPK with straw, NPKS; combined application of NPK with manure, NPKM). Results showed that straw addition strongly increased native SOC decomposition by 15–44%, inducing positive PEs across sites and fertilization treatments. Compared to CK treatment, the NPK and NPKS treatments significantly increased PE by 26% and 98%, respectively, in the UQ soil, but had little effect on the PE in the GZL soil. The NPKM treatment strongly decreased PE by 51–55%, mainly due to the increased proportion of mineral-associated organic carbon (MAOC) and N availability, and decreased fungal abundances, as compared to the CK treatment in UQ and GZL soils. The PE intensities were significantly lower in GZL soil (5.1–11.7 mg CO2-C/g SOC) relative to UQ soil (13.7–54.8 mg CO2-C/g SOC), primarily due to the higher MAOC/SOC ratio and N availability in the former across fertilization regimes. Overall, manure application has the potential to mitigate soil C loss via priming, mainly resulting from enhanced SOC stabilization via mineral protection and increased N availability, thus facilitating SOC sequestration in agroecosystems.

Lipoxygenase (LOX) holds significant promise for food and pharmaceutical industries. However, albeit its application has been hampered by low catalytic activity and suboptimal thermostability. To address the drawbacks, a directed evolution strategy was explored to enhance the catalytic activity and thermostability of LOX from Enterovibrio norvegicus (EnLOX) for the first time. After two rounds of error-prone polymerase chain reaction (error-prone PCR) and one generations of sequential DNA shuffling, all of four different mutants showed a significant increase in the specific activity of EnLOX, ranging from 132.07 ± 9.34 to 330.17 ± 18.54 U/mg. Among these mutants, D95E/T99A/A121H/S142N/N444W/S613G (EAHNWG) exhibited the highest specific activity, which was 8.25-fold higher than the wild-type enzyme (WT). Meanwhile, the catalytic efficiency (Kcat/Km) of EAHNWG was also improved, which was 13.61 ± 1.67 s−1 μM−1, in comparison to that of WT (4.83 ± 0.38 s−1 μM−1). In addition, mutant EAHNWG had a satisfied thermostability with the t1/2,50 °C value of 6.44 ± 0.24 h, which was 0.4 h longer than that of the WT. Furthermore, the molecular dynamics simulation and structural analysis demonstrated that the reduction of hydrogen bonds number, the enhancement of hydrophobic interactions in the catalytic pocket, and the improvement of flexibility of the lid domain facilitated structural stability and the strength of substrate binding capacity for improved thermal stability and catalytic efficiency of mutant LOX after directed evolution. Overall, these results could provide the guidance for further enzymatic modification of LOX with high catalytic performance for industrial application.

Background: The occurrence and disability of myocardial infarction (MI) are on the rise globally, making it a significant contributor to cardiovascular mortality. Irreversible myocardial apoptosis plays a crucial role in causing MI. Long non-coding RNAs (LncRNAs) are key regulators of the cardiac remodeling process. Therefore, it is necessary to explore the effect of LncRNAs on cardiomyocyte apoptosis in MI. Methods: The rat-MI model was constructed, LncRNA-Seq and qPCR analyses were used to determine differentially expressed genes obtained from heart tissue of rats in the MI and sham groups. The miRanda software was used to predict the binding sites of LncRNA-miRNA and miRNA-mRNA, which were futhrer verified by dual luciferase assay. The LncRNA-miRNA-apoptosis pathway was further validated using hypoxia-exposed primary cardiomyocytes. Results: Compared to the sham group, 412 LncRNAs were upregulated and 501 LncRNAs were downregulated in MI-rat heart tissues. Among them, LncRNA AC125982.2 was most significantly upregulated in MI-rat heart tissues and hypoxic cardiomyocytes. Knockdown of AC125982.2 and ATG4B expression reversed hypoxia-induced apoptosis. In addition, transfection of mir-450b-3p inhibitor attenuated the protective effect of AC125982.2 knockdown. Moreover, we found that AC125982.2 modulated ATG4B expression by acting as a sponge for miR-450b-3p. Conclusion: Upregulated AC125982.2 expression regulates ATG4B by sponging miR-450b-3p, promoting cardiomyocyte apoptosis and contributing to rat MI development.

AIM: To study the characteristics of new corneal biomechanical parameters in different degrees of myopia and analyze the correlation of the new parameter stress-strain index(SSI).METHODS: A cross-sectional study was conducted on 366 adult patients(718 eyes)with different degrees of myopia who received treatment at the First Affiliated Hospital of Dali University from October 2021 to November 2021, aged 18-50 years, and the spherical equivalent(SE)was -0.50～-16.75D. The axial length(AL)of the eye was measured by IOL master, and the new corneal biomechanical parameters, central corneal thickness(CCT)and intraocular pressure(IOP)were measured by corneal visualization Scheimpflug technology(Corvis ST). The subjects were categorized into low myopia, moderate myopia and high myopia groups according to SE. The data were analyzed by ANOVA and Pearson correlation.RESULTS: The ratio of the thinnest corneal thickness to horizontal thickness change rate(ARTh)and SSI were statistically significant(P0.05). SSI was positively correlated with age(r=0.102, P=0.006), SE(r=0.361, P0.05).CONCLUSION: With the increase of myopia degree and the elongation of the axial length, the SSI value becomes smaller and the corneal hardness decreases. SSI may be a helpful corneal biomechanical indicator for future research on myopia.

Abstract Aims To investigate the effect of a transition programme including cognitive‐behaviour‐based preceptorship intervention on ICU new graduate nurses' (NGNs)' professional identity and their intention to remain employed. Design One‐arm pre‐ and post‐test design followed the TREND Statement. Methods NGNs' professional identity and intention to remain employed were measured at baseline (T1), postintervention (1 month, T2) and 6‐month follow‐up (T3). Results Fifty‐three NGNs completed the programme, and their professional identity score significantly increased postintervention [from 111.5 (SD = 16.72) at T1 to 114.2 (SD = 9.12) at T2, p 0.05). The transition programme was effective to improve ICU NGNs' professional identity immediately after the intervention, but the increment did not maintain at the 6‐month follow‐up.

There is a low efficiency of A-to-G base conversion in at specific positions using base editors. Here the authors fuse ABE8e with the Rad51 DNA-binding domain to generate a hyperactive ABE allowing improved A-to-G editing efficiency at the region proximal to the PAM and improved simultaneous A/C conversion efficiency.

The clarification of the type of the ferrite formed owing to the melting of the Al–Si coating into the weld metal plays a significant role in the improvement of the mechanical properties of the laser welded joint. The results obtained by optical microscope (OM) and scanning electron microscope (SEM) in the regions near the ferrite before and after thermal simulation clearly demonstrate the negligible change in microstructure morphology, even for the ferrite with the size around 2 μm. In addition, simulated by JMatPro software, it can be found that the content of the α-ferrite decreases with the increase of the cooling rate. Based on the ultra-high cooling rate during laser welding and negligible change in the morphology of the ferrite by decreasing the cooling rate, the type of the ferrite formed in the WM is clarified as the δ-ferrite, without the formation of α-ferrite. The differences in the formation condition between the δ-ferrite and α-ferrite can affect the control of their size, morphology and distribution.

Abstract This paper first investigates the equivalence of the space and translation invariance of Stepanov-like doubly weighted pseudo almost automorphic stochastic processes for nonequivalent weight functions; secondly, based on semigroup theory, fractional calculations, and the Krasnoselskii fixed-point theorem, we obtain the existence and uniqueness of Stepanov-like doubly weighted pseudo almost automorphic mild solutions for a class of nonlinear fractional stochastic neutral functional differential equations under non-Lipschitz conditions. These results enrich the complex dynamics of Stepanov-like doubly weighted pseudo almost automorphic stochastic processes.