Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

ATPR induces acute promyelocytic leukemia cells differentiation and cycle arrest via the lncRNA CONCR/DDX11/PML-RARα signaling axis.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) with a high mortality rate, and the production of PML-RARα fusion protein is the cause of its pathogenesis. Our group has synthesized a novel compound, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), by structural modification of All-trans retinoic acid (ATRA), which has strong cell differentiation-inducing effects and inhibits the expression of PML-RARα. In this study, acute promyelocytic leukemia NB4 cells before and after ATPR induction were analyzed by whole transcriptome microarray, and the expression of lncRNA CONCR was found to be significantly downregulated. The role of CONCR in ATPR-induced cell differentiation and cycle arrest was explored through overexpression and silencing of CONCR. And then the database was used to predict that CONCR may bind to DEAD/H-Box Helicase 11 (DDX11) protein to further explore the role of CONCR binding to DDX11. The results showed that ATPR could reduce the expression of CONCR, and overexpression of CONCR could reverse the ATPR-induced cell differentiation and cycle blocking effect, and conversely silencing of CONCR could promote this effect. RNA immunoprecipitation (RIP) experiments showed that CONCR could bind to DDX11, the protein expression levels of DDX11 and PML-RARα were elevated after overexpression of CONCR. These results suggest that ATPR can regulate the expression of DDX11 through CONCR to affect the expression of PML-RARα fusion protein, which in turn induces the differentiation and maturation of APL cells.

Prediction model and its application of helium extraction OPEX based on response surface methodology.

Focusing on the situation of the low helium content in natural gas resource in China and the high cost of helium extraction, the OPEX prediction model of helium extraction that based on the Response Surface Methodology (RSM) is proposed. This method applies ASPEN-HYSYS software to simulate the helium extraction process flow for a given product composition, pressure, and temperature; Applying the Design Expert module for Response Surface Methodology(RSM) parameter design, combined with OPEX of existing projects, determine the key influencing factors and upper and lower limits of OPEX, and obtaining the corresponding OPEX for different parameter values; Applying the Box Behnken Design (BBD) principle to optimize the helium extraction process parameters of RSM, based on fitting results and parameter significance verification of second-order regression function, the OPEX prediction model is built.This method is applied to a domestic helium extraction project, and the unit helium extraction cost is between 100 and 119.52 yuan/m3, IRR is 13.37%. The result shows the project has economic benefit, and the method presents a good perspective application.

Twenty years of research on borderline personality disorder: a scientometric analysis of hotspots, bursts, and research trends.

Borderline personality disorder (BPD), a complex and severe psychiatric disorder, has become a topic of considerable interest to current researchers due to its high incidence and severity of consequences. There is a lack of a bibliometric analysis to visualize the history and developmental trends of researches in BPD. We retrieved 7919 relevant publications on the Web of Science platform and analyzed them using software CiteSpace (6.2.R4). The results showed that there has been an overall upward trend in research interest in BPD over the past two decades. Current research trends in BPD include neuroimaging, biological mechanisms, and cognitive, behavioral, and pathological studies. Recent trends have been identified as "prevention and early intervention", "non-pharmacological treatment" and "pathogenesis". The results are like a reference program that will help determine future research directions and priorities.

A scientometric review of the growing trends in transcranial alternating current stimulation (tACS).

Objective: The aim of the current study was to provide a comprehensive picture of tACS-related research in the last decade through a bibliometric approach in order to systematically analyze the current status and cutting-edge trends in this field. Methods: Articles and review articles related to tACS from 2013 to 2022 were searched on the Web of Science platform. A bibliometric analysis of authors, journals, countries, institutions, references, and keywords was performed using CiteSpace (6.2.R2), VOSviewer (1.6.19), Scimago Graphica (1.0.30), and Bibliometrix (4.2.2). Results: A total of 602 papers were included. There was an overall increase in annual relevant publications in the last decade. The most contributing author was Christoph S. Herrmann. Brain Stimulation was the most prolific journal. The most prolific countries and institutions were Germany and Harvard University, respectively. Conclusion: The findings reveal the development prospects and future directions of tACS and provide valuable references for researchers in the field. In recent years, the keywords "gamma," "transcranial direct current simulation," and "Alzheimer's disease" that have erupted, as well as many references cited in the outbreak, have provided certain clues for the mining of research prefaces. This will act as a guide for future researchers in determining the path of tACS research.

Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair.

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.

Antiadhesion Biomaterials in Tendon Repair: Application Status and Future Prospect.

The healing process after tendon injury is often accompanied by the formation of peritendinous adhesion, contributing to limb dysfunction and exerting detrimental effects on the individuals, as well as the development of society and economy. With the continuous development of material science, as well as the augmented understanding of tendon healing and the mechanism of peritendinous adhesion formation, materials used for the fabrication of barrier membranes against peritendinous adhesion emerge endlessly. In this article, based on the analysis of the mechanism of adhesion formation, we first review the commonly used natural and synthetic materials, along with their corresponding fabrication strategies, in order to furnish valuable insights for the future optimization and development of antiperitendinous adhesion barrier membranes. This article also discusses the interaction between antiadhesion materials and cells for ameliorating peritendinous adhesion.

Highly birefringent side-hole fiber Bragg grating for high-temperature pressure sensing.

We demonstrate a novel, to the best of our knowledge, high-temperature pressure sensor based on a highly birefringent fiber Bragg grating (Hi-Bi FBG) fabricated in a dual side-hole fiber (DSHF). The Hi-Bi FBG is generated by a femtosecond laser directly written sawtooth structure in the DSHF cladding along the fiber core through the slow axis (i.e., the direction perpendicular to the dual-hole axis). The sawtooth structure serves as an in-fiber stressor and also generates Bragg resonance due to its periodicity. The DSHF was etched by hydrofluoric acid to increase its pressure sensitivity, and the diameter of two air holes was enlarged from 38.2 to 49.6 µm. A Hi-Bi FBG with a birefringence of up to 1.8 × 10-3 was successfully created in the etched DSHF. Two distinct reflection peaks could be observed by using a commercial FBG interrogator. Moreover, pressure measurement from 0 to 3 MPa at a high temperature of 700°C was conducted by monitoring the birefringence-induced peak splits and achieved a high-pressure sensitivity of -21.2 pm/MPa. The discrimination of the temperature and pressure could be realized by simultaneously measuring the Bragg wavelength shifts and peak splits. Furthermore, a wavelength-division-multiplexed (WDM) Hi-Bi FBG array was also constructed in the DSHF and was used for quasi-distributed high-pressure sensing up to 3 MPa. As such, the proposed femtosecond laser-inscribed Hi-Bi FBG is a promising tool for high-temperature pressure sensing in harsh environments, such as aerospace vehicles, nuclear reactors, and petrochemical industries.

Palliative primary tumor resection may not offer survival benefits for patients with unresectable metastatic colorectal neuroendocrine neoplasms, one multicenter retrospective cohort study.

BACKGROUND: The efficacy of palliative primary tumor resection (PTR) in improving prognosis for patients with unresectable metastatic colorectal neuroendocrine neoplasms (NENs) has not been fully explored. METHODS: We performed one retrospective cohort study and recruited 68 patients with unresectable metastatic colorectal NENs from two Chinese medical centers between 2000 and 2022. All patients were assigned to PTR group and no PTR group. The clinicopathological manifestation data were carefully collected, and the survival outcomes were compared between the two groups using Kaplan-Meier methods. Propensity score matching (PSM) was conducted to minimize confounding bias. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: A total of 32 patients received PTR, and the other 36 patients did not. The median progression-free survival (PFS) and overall survival (OS) times were 4 and 22 months in the whole cohort, respectively. For patients who received no PTR, the median OS was 16 months, and the 1-year OS rate and 3-year OS rate were 56.4% and 39.6%, respectively. For patients who received PTR, the median OS was 24 months, and the 1-year OS rate and 3-year OS rate were 67.9% and 34.1%, respectively. However, the Kaplan-Meier survival curves and log-rank test demonstrated no significant survival difference between the two groups (P = 0.963). Moreover, palliative PTR was also not confirmed as a prognostic factor in subsequent univariable and multivariable Cox proportional hazards regression analyses in both the original and matched cohorts. Only histological differentiation was identified as an independent prognostic factor affecting PFS [hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.02-3.41, P = 0.043] and OS [HR = 3.70, 95% CI: 1.09-12.48, P = 0.035] in the original cohort. CONCLUSIONS: Palliative PTR may not offer survival benefits for patients with unresectable metastatic colorectal NENs.

Long-Acting Heterodimeric Paclitaxel-Idebenone Prodrug-Based Nanomedicine Promotes Functional Recovery after Spinal Cord Injury.

After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood-spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel-idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI.

Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers.

Tissue adhesion is one of the most common postoperative complications, which is frequently accompanied by inflammation, pain, and even dyskinesia, significantly reducing the quality of life of patients. Thus, to prevent the formation of tissue adhesions, various strategies have been explored. Among these methods, placing anti-adhesion membranes over the injured site to separate the wound from surrounding tissues is a simple and prominently favored method. Recently, electrospun nanofibers have been the most frequently investigated antiadhesive membranes due to their tunable porous structure and high porosities. They not only can act as an essential barrier and functional carrier system but also allow for high permeability and nutrient transport, showing great potential for preventing tissue adhesion. Herein, we provide a short review of the most recent applications of electrospun nanofibrous antiadhesive membranes in tendons, the abdominal cavity, dural sac, pericardium, and meninges. Firstly, each section highlights the most representative examples and they are sorted based on the latest progress of related research. Moreover, the design principles, preparation strategies, overall performances, and existing problems are highlighted and evaluated. Finally, the current challenges and several future ways to develop electrospun nanofibrous antiadhesive membranes are proposed. The systematic discussion and proposed directions can shed light on ideas and guide the reasonable design of electrospun nanofibrous membranes, contributing to the development of exceptional tissue anti-adhesive materials in the foreseeable future.

Neuromorphic electro-stimulation based on atomically thin semiconductor for damage-free inflammation inhibition.

Inflammation, caused by accumulation of inflammatory cytokines from immunocytes, is prevalent in a variety of diseases. Electro-stimulation emerges as a promising candidate for inflammatory inhibition. Although electroacupuncture is free from surgical injury, it faces the challenges of imprecise pathways/current spikes, and insufficiently defined mechanisms, while non-optimal pathway or spike would require high current amplitude, which makes electro-stimulation usually accompanied by damage and complications. Here, we propose a neuromorphic electro-stimulation based on atomically thin semiconductor floating-gate memory interdigital circuit. Direct stimulation is achieved by wrapping sympathetic chain with flexible electrodes and floating-gate memory are programmable to fire bionic spikes, thus minimizing nerve damage. A substantial decrease (73.5%) in inflammatory cytokine IL-6 occurred, which also enabled better efficacy than commercial stimulator at record-low currents with damage-free to sympathetic neurons. Additionally, using transgenic mice, the anti-inflammation effect is determined by ß2 adrenergic signaling from myeloid cell lineage (monocytes/macrophages and granulocytes).

Transcriptomic and Metabolomic Analyses Reveal the Role of Phenylalanine Metabolism in the Maize Response to Stalk Rot Caused by Fusarium proliferatum.

Stalk rot is a prevalent disease of maize (Zea mays L.) that severely affects maize yield and quality worldwide. The ascomycete fungus Fusarium spp. is the most common pathogen of maize stalk rot. At present, the molecular mechanism of Fusarium proliferation during the maize stalk infection that causes maize stalk rot has rarely been reported. In this study, we investigated the response of maize to F. proliferatum infestation by analyzing the phenotypic, transcriptomic, and metabolomic data of inbred lines ZC17 (resistant) and CH72 (susceptible) with different levels of resistance to stalk rot. Physiological and phenotypic results showed that the infection CH72 was significantly more severe than ZC17 after inoculation. Transcriptome analysis showed that after inoculation, the number of differentially expressed genes (DEGs) was higher in CH72 than in ZC17. Nearly half of these DEGs showed the same expression trend in the two inbred lines. Functional annotation and enrichment analyses indicated that the major pathways enriched for DEGs and DEMs included the biosynthesis of plant secondary metabolites, phenylalanine metabolism, biosynthesis of plant hormones, and plant-pathogen interactions. The comprehensive analysis of transcriptome and metabolome data indicated that phenylalanine metabolism and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways played a crucial role in maize resistance to F. proliferatum infection. In addition, a transcription factor (TF) analysis of the DEGs showed that several TF families, including MYB, bHLH, NAC, and WRKY, were significantly activated after inoculation, suggesting that these TFs play important roles in the molecular regulatory network of maize disease resistance. The findings of this study provide valuable insights into the molecular basis of the response of maize to Fusarium proliferatum infection and highlight the importance of combining multiple approaches, such as phenotyping, transcriptomics, and metabolomics, to gain a comprehensive understanding of plant-pathogen interactions.

Targeted Macrophage CRISPR-Cas13 mRNA Editing in Immunotherapy for Tendon Injury.

CRISPR-Cas13 holds substantial promise for tissue repair through its RNA editing capabilities and swift catabolism. However, conventional delivery methods fall short in addressing the heightened inflammatory response orchestrated by macrophages during the acute stages of tendon injury. In this investigation, macrophage-targeting cationic polymers are systematically screened to facilitate the entry of Cas13 ribonucleic-protein complex (Cas13 RNP) into macrophages. Notably, SPP1 (OPN encoding)-producing macrophages are recognized as a profibrotic subtype that emerges during the inflammatory stage. By employing ROS-responsive release mechanisms tailored for macrophage-targeted Cas13 RNP editing systems, the overactivation of SPP1 is curbed in the face of an acute immune microenvironment. Upon encapsulating this composite membrane around the tendon injury site, the macrophage-targeted Cas13 RNP effectively curtails the emergence of injury-induced SPP1-producing macrophages in the acute phase, leading to diminished fibroblast activation and mitigated peritendinous adhesion. Consequently, this study furnishes a swift RNA editing strategy for macrophages in the inflammatory phase triggered by ROS in tendon injury, along with a pioneering macrophage-targeted carrier proficient in delivering Cas13 into macrophages efficiently.

Optimized helical intermedium-period fiber grating for breathing monitoring.

The investigation into the spectral properties and refractive index (RI) sensitivities at low RI region of helical intermedium-period fiber gratings (HIPFGs) with varied periods ranging from 10-48 µm is presented in detail for the first time. The structure of HIPFG is optimized for RI sensing in the RI range of 1.3-1.33 by comparing the optical properties of HIPFGs with different grating periods. The HIPFG with optimized structure is demonstrated to have a high average sensitivity of 302.5 nm/RIU in the RI ranging from 1.3 to 1.33, which is two orders more elevated than the traditional long-period fiber gratings. The improved HIPFG is also experimentally applied to breath monitoring in different states. Normal breath, slow breath, fast breath, and unhealthy breath are distinguished based on breathing rate, intensity, and time of exhalation and inhalation. The fastest response time is determined to be 10 ms. The results demonstrate that the optical fiber's sensitivity in the low RI region can be increased by shortening its period, offering a special strategy for improving detection performance of HIPFGs. By verifying its performance in breathing monitoring, it is proved that the optimized HIPFG sensor has the great potential to expand medical applications.

Peritendinous adhesion: Therapeutic targets and progress of drug therapy.

Peritendinous adhesion (PA) is one of the most common complications following hand surgery and characterized with abnormal hyperplasia of connective tissue and excessive deposition of extracellular matrix. Subsequently, various clinical symptoms such as chronic pain, limb dyskinesia and even joint stiffness occur and patients are always involved in the vicious cycle of "adhesion - release - re-adhesion", which seriously compromise the quality of life. Until present, the underlying mechanism remains controversial and lack of specific treatment, with symptomatic treatment being the only option to relieve symptoms, but not contributing no more to the fundamentally rehabilitation of basic structure and function. Recently, novel strategies have been proposed to inhibit the formation of adhesion tissues including implantation of anti-adhesion barriers, anti-inflammation, restraint of myofibroblast transformation and regulation of collagen overproduction. Furthermore, gene therapy has also been considered as a promising anti-adhesion treatment. In this review, we provide an overview of anti-adhesion targets and relevant drugs to summarize the potential pharmacological roles and present subsequent challenges and prospects of anti-adhesion drugs.

Effects of liposomal bupivacaine in preoperative fascia iliac block on postoperative pain and delirium in elderly patients undergoing hip fracture surgery: a study protocol for a randomised, parallel controlled prospective clinical study.

INTRODUCTION: Postoperative delirium (POD) is the most common acute fluctuating mental state change after hip fractures in older adults. Postoperative pain is a Grade A risk factor for POD and is closely related to the prognosis of patients undergoing hip fracture surgery. The fascia iliac block has a definite analgesic effect and few side effects, and several studies have reported that it reduces the occurrence of POD in patients undergoing general anaesthesia for hip fracture surgery. Liposomal bupivacaine is a local anaesthetic with a long half-life that significantly reduces the use of opioids and is conducive to patient prognosis and recovery. However, whether regional nerve block analgesia can decrease the occurrence of POD in elderly patients undergoing hip fracture surgery has not been reported. METHODS AND ANALYSIS: This is a single-blinded, randomised, parallel-controlled prospective clinical study. Participants will be randomly assigned preoperatively to either the liposomal bupivacaine (ie, Exparel) or ropivacaine groups by block randomisation. Then, the occurrence of POD (primary outcome) and postoperative pain (secondary outcome) will be evaluated. ETHICS AND DISSEMINATION: This research protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 guidelines and is approved by the Ethics Committee of Shanghai General Hospital (ID 2023-437). The original data are expected to be released in July 2029 on the ResMan original data-sharing platform (IPD-sharing platform) of the China Clinical Trial Registry, which can be viewed on the following website: http://www.medresman.org.cn. PROSPERO REGISTRATION NUMBER: ChiCTR2300074022.

How Impulsivity is Associated with Adolescent Depression: The Role of Substance Use, Gender and Social Support.

Background: Some risk/protective factors of adolescent depression have been proposed but have not been comprehensively studied. Recent advances in neuroimaging techniques have provided greater insight into the underlying neuropsychiatric mechanisms of depression-related factors such as impulsivity, substance use, gender difference and social support. However, how these factors are interconnected and how they affect depression in the real world is poorly understood. This study aimed to explore the relationships between adolescent depression with trait impulsivity, substance use and gender. We also tested the hypothesis that social support may play a buffering role in preventing depression. By expanding the diathesis-stress model. Methods: The adolescents enrolled in this study were grade 1 senior high school students from northern Taiwan (N = 5879), and they were assessed for depression, trait impulsivity, and tobacco/alcohol use. Hierarchical multiple linear regression was performed to control possible confounders, including other depression-related diathesis and sociodemographic variables. Gender differences were also analyzed by separately examining variables significantly associated with depression. Results: A higher level of depression was associated with female gender, trait impulsivity, low self-esteem, negative attitude towards the future, tobacco use, alcohol use, family discord and difficulty in basic family needs. Good parental health, living with their biological family and social support were protective factors. Trait impulsivity was significantly associated with depression after controlling for the confounding factors. Gender-specific analysis showed that trait impulsivity and tobacco use had a significant synergistic interaction on female depression. Social support from parents/peers was significantly associated with depression, but social support from other family members/teachers was not. Conclusion: The current study advances the understanding of adolescent depression and highlights that trait impulsivity, addictive substance use, social support and their interaction may play an influential role in the emergence of adolescent depression. Gender-specific research and treatment approach are also crucial, and more investigations are necessary.

The long-acting walking control of a cockroach bio-bot for vision-aided pipeline navigation.

Many small bionic crawling robots have been invented for search and rescue missions in narrow spaces. However, their locomotion capability is far from that of insects of the same size. Transforming a cockroach into a bio-bot has been a hot topic in the past decade. Herein, we modified this insect to perform surveillance work in dark confined environments. The synergistic electrical stimulation for turning control was proposed by alternating electrical stimulation of the cerci and antennae every 5 trials. The result showed that this method was able to control cockroaches turning steadily 117 times. An electronic backpack was designed, which was capable of transmitting images in real time, and a light emitting diode (LED) was installed on the backpack providing a light source for the camera. Thus, a vision-aided navigation system was formed for dark confined environments, e.g. pipelines. With a host computer software, the operator controlled the bio-bot to pass through a completely dark and closed pipeline. The electronic backpack and the host computer were connected via transmission control protocol (TCP), which allows the operator to manipulate the bio-robot remotely. This technology can be applied in pipeline surveillance in the future.