Characterization of the Dynamic Behavior of Multinanobubble System under Shock Wave Influence.

Shockwave-induced changes in nanobubbles cause cavitation erosion and membrane damage but can also be applied to biocarrier transport. Currently, research focuses on single nanobubbles; however, in reality, nanobubbles usually appear as a multibubble system. Therefore, this study proposes a method based on cutting and replicating to construct a multibubble model. This method can be widely applied to molecular dynamics (MD) models and enhance the customization capabilities of MD models. The dynamic behavior of a multinanobubble system with different numbers and arrangements of nanobubbles is investigated with the MD method under the influence of shock waves in a liquid argon system. The study also explores the range of influence between nanobubbles. The results show that in the case of two nanobubbles, when the distance between the bubbles is constant, the smaller the angle between the direction of the shock wave and the line connecting the bubbles, the greater is the influence between nanobubbles, and the moment of collapse of the nanobubbles farther away from the shock wave is slower. When three nanobubbles are arranged with a right offset, after the first bubble collapses, the effect on the other two bubbles is similar to the changes in bubbles when the angle of arrangement is 30° or 60°. Under a different arrangement, the change of shock wave velocity on the nanobubble size only affects its collapse time and contraction collapse rate. When the shock wave with a radian of about 2.87 or greater than 2.87 touches the bubbles, the collapse of the second nanobubble will not be affected.

Delta like 4 regulates cerebrovascular development and endothelial integrity via DLL4-NOTCH-CLDN5 pathway and is vulnerable to neonatal hyperoxia.

The mechanisms governing brain vascularization during development remain poorly understood. A key regulator of developmental vascularization is delta like 4 (DLL4), a Notch ligand prominently expressed in endothelial cells (EC). Exposure to hyperoxia in premature infants can disrupt the development and functions of cerebral blood vessels and lead to long-term cognitive impairment. However, its role in cerebral vascular development and the impact of postnatal hyperoxia on DLL4 expression in mouse brain EC have not been explored. We determined the DLL4 expression pattern and its downstream signalling gene expression in brain EC using Dll4+/+ and Dll4+/LacZ mice. We also performed in vitro studies using human brain microvascular endothelial cells. Finally, we determined Dll4 and Cldn5 expression in mouse brain EC exposed to postnatal hyperoxia. DLL4 is expressed in various cell types, with EC being the predominant one in immature brains. Moreover, DLL4 deficiency leads to persistent abnormalities in brain microvasculature and increased vascular permeability both in vivo and in vitro. We have identified that DLL4 insufficiency compromises endothelial integrity through the NOTCH-NICD-RBPJ-CLDN5 pathway, resulting in the downregulation of the tight junction protein claudin 5 (CLDN5). Finally, exposure to neonatal hyperoxia reduces DLL4 and CLDN5 expression in developing mouse brain EC. We reveal that DLL4 is indispensable for brain vascular development and maintaining the blood-brain barrier's function and is repressed by neonatal hyperoxia. We speculate that reduced DLL4 signalling in brain EC may contribute to the impaired brain development observed in neonates exposed to hyperoxia. KEY POINTS: The role of delta like 4 (DLL4), a Notch ligand in vascular endothelial cells, in brain vascular development and functions remains unknown. We demonstrate that DLL4 is expressed at a high level during postnatal brain development in immature brains and DLL4 insufficiency leads to abnormal cerebral vasculature and increases vascular permeability both in vivo and in vitro. We identify that DLL4  regulates endothelial integrity through NOTCH-NICD-RBPJ-CLDN5 signalling. Dll4 and Cldn5 expression are decreased in mouse brain endothelial cells exposed to postnatal hyperoxia.

Network analysis of posttraumatic stress and posttraumatic growth symptoms among women in subsequent pregnancies following pregnancy loss.

BACKGROUND: Pregnant women who have undergone pregnancy loss often display both posttraumatic stress (PTS) and posttraumatic growth (PTG). However, the precise relationship and structure of symptomatic levels of PTS and PTG have not been well understood. This study aimed to assess the associations between PTS and PTG symptoms in women during subsequent pregnancies following a previous pregnancy loss. METHODS: A total of 406 pregnant women with a history of pregnancy loss were included in this study. The Impact of Events Scale-6 (IES-6) and the Posttraumatic Growth Inventory Short Form (PTGI-SF) were used to assess symptoms of PTS and PTG, respectively. The Graphical Gaussian Model was employed to estimate the network model. Central symptoms and bridge symptoms were identified based on "expected influence" and "bridge expected influence" indices, respectively. The stability and accuracy of the network were examined using the case-dropping procedure and nonparametric bootstrapped procedure. RESULTS: The network analysis identified PTG3 ("Ability to do better things") as the most central symptom, followed by PTS3 ("Avoidance of thoughts") and PTG6 ("New path for life") in the sample. Additionally, PTS3 ("Avoidance of thoughts") and PTG9 ("Perception of greater personal strength") were bridge symptoms linking PTS and PTG clusters. The network structure was robust in stability and accuracy tests. CONCLUSIONS: Interventions targeting the central symptoms identified, along with key bridge symptoms, have the potential to alleviate the severity of PTS experienced by women with a history of pregnancy loss and promote their personal growth.

Biochar dose-dependent impacts on soil bacterial and fungal diversity across the globe.

Biochar, a widely used material for soil amendment, has been found to offer numerous advantages in improving soil properties and the habitats for soil microorganisms. However, there is still a lack of global perspectives on the influence of various levels of biochar addition on soil microbial diversity and primary components. Thus, in our study, we performed a global meta-analysis of studies to determine how different doses of biochar affect soil total carbon (C), nitrogen (N), pH, alpha- and beta-diversity, and the major phyla of both bacterial and fungal communities. Our results revealed that biochar significantly increased soil pH by 4 %, soil total C and N by 68 % and 22 %, respectively, in which the positive effects increased with biochar doses. Moreover, biochar promoted soil bacterial richness and evenness by 3-8 % at the biochar concentrations of 1-5 % (w/w), while dramatically shifting bacterial beta-diversity at the doses of >2 % (w/w). Specifically, biochar exhibited significantly positive effects on bacterial phyla of Acidobacteria, Bacteroidetes, Gemmatimonadetes, and Proteobacteria, especially Deltaproteobacteria and Gammaproteobacteria, by 4-10 % depending on the concentrations. On the contrary, the bacterial phylum of Verrucomicrobia and fungal phylum of Basidiomycota showed significant negative responses to biochar by -8 % and -24 %, respectively. Therefore, our meta-analysis provides theoretical support for the development of optimized agricultural management practices by emphasizing biochar application dosing.

Wavelength dependency and photosensitizer effects in UV-LED photodegradation of iohexol.

Iodinated X-ray contrast media (ICM) are ubiquitously present in water sources and challenging to eliminate using conventional processes, posing a significant risk to aquatic ecosystems. Ultraviolet light-emitting diodes (UV-LED) emerge as a promising technology for transforming micropollutants in water, boasting advantages such as diverse wavelengths, elimination of chemical additives, and no induction of microorganisms' resistance to disinfectants. The research reveals that iohexol (IOX) degradation escalates as UV wavelength decreases, attributed to enhanced photon utilization efficiency. Pseudo-first-order rate constants (kobs) were determined as 3.70, 2.60, 1.31 and 0.65 cm2 J-1 at UV-LED wavelengths of 255, 265, 275 and 285 nm, respectively. The optical properties of dissolved organic matter (DOM) and anions undeniably influence the UV-LED photolysis process through photon competition and the generation of reactive substances. The influence of Cl- on IOX degradation was insignificant at UV-LED 255, but it promoted IOX degradation at 265, 275 and 285 nm. IOX degradation was accelerated by ClO2-, NO3-and HA due to the formation of various reactive species. In the presence of NO3-, the kobs of IOX followed the order: 265 > 255 > 275 > 285 nm. Photosensitizers altered the spectral dependence of IOX, and the intermediate photoactivity products were detected using electron spin resonance. The transformation pathways of IOX were determined through density functional theory calculations and experiments. Disinfection by-products (DBPs) yields of IOX during UV-LED irradiation decreased as the wavelength increased: 255 > 265 > 275 > 285 nm. The cytotoxicity index value decreased as the UV-LED wavelength increased from 255 to 285 nm. These findings are crucial for selecting the most efficient wavelength for UV-LED degradation of ICM and will benefit future water purification design.

Therapeutic role of neural stem cells in neurological diseases.

The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges.

Associations between pregnancy loss and common mental disorders in women: a large prospective cohort study.

Background: Increasing evidence suggests that pregnancy loss can lead to negative emotional outcomes, such as anxiety and depression, for women. However, limited knowledge exists regarding the long-term risk of mental disorders among individuals who have experienced pregnancy loss. Objective: To investigate the associations between pregnancy loss and the risk of common mental disorders. Methods: In the UK Biobank, a total of 218,990 women without any mental disorder at baseline were enrolled between 2006 and 2010 and followed until October 2022. Information on the history of pregnancy loss was obtained through self-reported questionnaires at baseline. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between pregnancy loss and common mental disorders. Results: During a median follow-up time of 13.36 years, there were 26,930 incident cases of common mental disorders. Incidence rates of common mental disorders were elevated among women with a history of stillbirth (HR 1.15, 95% CI: 1.07-1.23), miscarriage (HR 1.06, 95% CI: 1.02-1.10), or pregnancy termination (HR 1.21, 95% CI: 1.17-1.25) compared to those without such experiences. Furthermore, the risk of common mental disorders significantly increased in women with two or more miscarriages (HR 1.14, 95% CI: 1.08-1.19) or two or more pregnancy terminations (HR 1.39, 95% CI: 1.30-1.48). Conclusions: Pregnancy loss is associated with an increased risk of common mental disorders in women later in life. These findings may contribute to the enhancement of long-term monitoring and prevention of common mental disorders for women with such a history.

Construction of Oxygen Vacancy-Rich TiO2 Nanocrystals for Boosting the Ammonolysis of Caprolactam to 6-Aminocapronitrile.

Hexamethylene diamine, an important chemical intermediate for polyamides, can be synthesized through the two-step route of caprolactam (CPL) ammonolysis to 6-aminocapronitrile (ACN), followed by hydrogenation. This method has received increasing attention from academia and industry. However, studies on the catalyst structure-performance correlation in CPL ammonolysis are still sporadic. In this work, a series of anatase TiO2 with different oxygen vacancy concentrations was prepared by chemical reduction using NaBH4. The oxygen vacancy on TiO2 surface, presented as Ti3+ sites, substantially enhances the adsorption and activation of NH3, which are demonstrated as the key steps in ammonolysis. Owing to the synergistic effect of Ti3+ and Ti4+ species, the CPL conversion rate and ACN selectivity of 85 and 97%, respectively, are achieved within 250 h. Density functional theory calculations showed that the intermediates on oxygen vacancy-rich TiO2 had a more favorable adsorption energy compared to those on intact TiO2, which is in good agreement with the experimental results.

Quantitative proteomics of the miR-301a/SOCS3/STAT3 axis reveals underlying autism and anxiety-like behavior.

Autism is a widespread neurodevelopmental disorder. Although the research on autism spectrum disorders has been increasing in the past decade, there is still no specific answer to its mechanism of action and treatment. As a pro-inflammatory microRNA, miR-301a is abnormally expressed in various psychiatric diseases including autism. Here, we show that miR-301a deletion and inhibition exhibited two distinct abnormal behavioral phenotypes in mice. We observed that miR-301a deletion in mice impaired learning/memory, and enhanced anxiety. On the contrary, miR-301a inhibition effectively reduced the maternal immune activation (MIA)-induced autism-like behaviors in mice. We further demonstrated that miR-301a bound to the 3'UTR region of the SOCS3, and that inhibition of miR-301a led to the upregulation of SOCS3 in hippocampus. The last result in the reduction of the inflammatory response by inhibiting phosphorylation of AKT and STAT3, and the expression level of IL-17A in poly(I:C)-induced autism-like features in mice. The obtained data revealed the miR-301a as a critical participant in partial behavior phenotypes, which may exhibit a divergent role between gene knockout and knockdown. Our findings ascertain that miR-301a negatively regulates SOCS3 in MIA-induced autism in mice and could present a new therapeutic target for ameliorating the behavioral abnormalities of autism.

Genome-wide characterization of the CPA gene family in potato and a preliminary functional analysis of its role in NaCl tolerance.

BACKGROUND: The cation/proton antiporter (CPA) superfamily plays a crucial role in regulating ion homeostasis and pH in plant cells, contributing to stress resistance. However, in potato (Solanum tuberosum L.), systematic identification and analysis of CPA genes are lacking. RESULTS: A total of 33 StCPA members were identified and classified into StNHX (n = 7), StKEA (n = 6), and StCHX (n = 20) subfamilies. StCHX owned the highest number of conserved motifs, followed by StKEA and StNHX. The StNHX and StKEA subfamilies owned more exons than StCHX. NaCl stress induced the differentially expression of 19 genes in roots or leaves, among which StCHX14 and StCHX16 were specifically induced in leaves, while StCHX2 and StCHX19 were specifically expressed in the roots. A total of 11 strongly responded genes were further verified by qPCR. Six CPA family members, StNHX1, StNHX2, StNHX3, StNHX5, StNHX6 and StCHX19, were proved to transport Na+ through yeast complementation experiments. CONCLUSIONS: This study provides comprehensive insights into StCPAs and their response to NaCl stress, facilitating further functional characterization.

Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non-heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity. METHODS: Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest. RESULTS: Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P=0.020) and lower sympathetic baroreflex sensitivity (-2.83±0.76 versus -3.57±1.19 bursts/100 heartbeats/mm Hg; P=0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P=0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P=0.135-0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P<0.001) compared with controls. CONCLUSIONS: Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.

High-performance plastic-derived metal-free catalysts for organic pollutants degradation via Fenton-like reaction.

The preparation of waste plastics-derived catalysts is an effective strategy for the waste reclamation. However, plastic-derived material is unsuitable for wastewater purification due to its small specific surface area (SSA) and inadequate active sites (such as N/O sites). Herein, we synthesized graphene-like nanosheets using g-C3N4 as the self-sacrificing soft template and plastic as the carbon precursor. Consequently, this strategy greatly promoted the efficiencies of the emerging organic pollutants degradation with the SSA and N content of the plastic-derived biochar increasing up to 1043.4 m2/g and 17.53 at.%, respectively. In detail, 100 % sulfadiazine (SD) removal could be achieved in 180 s via the activation of peroxymonosulfate (PMS) and the catalytic activity is far higher than previous research. Mechanism experiments corroborated that such a striking performance was attributed to the generation of SO4•-, O2•- and 1O2. Meanwhile, kinds of plastic precursors, even medical waste (i.e., masks, gauze, operating caps and degreasing cotton) were also applicable. And the practical application of the plastic-derived catalyst was further demonstrated by treating pollutants in a continuous flow mode with in situ fabricated membrane. This work provides valuable insights into waste plastics processing and water pollutants removal.

The role of olfactory ensheathing cells in the repair of nerve injury.

Cell transplantation has brought about a breakthrough in the treatment of nerve injuries, and the efficacy of cell transplantation compared to drug and surgical therapies is very exciting. In terms of transplantation targets, the classic cells include neural stem cells (NSCs) and Schwann cells, while a class of cells that can exist and renew throughout the life of the nervous system - olfactory ensheathing cells (OECs) - has recently been discovered in the olfactory system. OECs not only encircle the olfactory nerves but also act as macrophages and play an innate immune role. OECs can also undergo reprogramming to transform into neurons and survive and mature after transplantation. Currently, many studies have confirmed the repairing effect of OECs after transplantation into injured nerves, and safe and effective results have been obtained in clinical trials. However, the specific repair mechanism of OECs among them is not quite clear. For this purpose, we focus here on the repair mechanisms of OECs, which are summarized as follows: neuroprotection, secretion of bioactive factors, limitation of inflammation and immune regulation, promotion of myelin and axonal regeneration, and promotion of vascular proliferation. In addition, integrating the aspects of harvesting, purification, and prognosis, we found that OECs may be more suitable for transplantation than NSCs and Schwann cells, but this does not completely discard the value of these classical cells. Overall, OECs are considered to be one of the most promising transplantation targets for the treatment of nerve injury disorders.

Experimental Study and Mechanism Analysis of Paraffin/Sisal Composite Phase Change Energy Storage Fiber Prepared by Vacuum Adsorption Method.

Sisal fiber exhibits a fibrous and porous structure with significant surface roughness, making it highly suitable for storing phase change materials (PCMs). Its intricate morphology further aids in mitigating the risk of PCM leakage. This research successfully employs vacuum adsorption to encapsulate paraffin within sisal fiber, yielding a potentially cost-effective, durable, and environmentally friendly phase change energy storage medium. A systematic investigation was carried out to evaluate the effects of sisal-to-paraffin mass ratio, fiber length, vacuum level, and negative pressure duration on the loading rate of paraffin. The experimental results demonstrate that a paraffin loading rate of 8 wt% can be achieved by subjecting a 3 mm sisal fiber to vacuum adsorption with 16 wt% paraffin for 1 h at -0.1 MPa. Through the utilization of nano-CT imaging enhancement technology, along with petrographic microscopy, this study elucidates the mechanism underlying paraffin storage within sisal fiber during vacuum adsorption. The observations reveal that a substantial portion of paraffin is primarily stored within the pores of the fiber, while a smaller quantity is firmly adsorbed onto its surface, thus yielding a durable phase change energy storage medium. The research findings contribute to both the theoretical foundations and the available practical guidance for the fabrication and implementation of paraffin/sisal fiber composite phase change energy storage mediums.

Rapid authentication of characteristic milk powders by recombinase polymerase amplification assays.

The authentication of dairy species has great significance for food safety. This study focused on a more rapid method for identifying major dairy species, and specific recombinase polymerase amplification (RPA)-based assays for cattle, goat, sheep, camel and donkey were developed. Through the developed RPA-based assays, goats and sheep could be simultaneously identified and bovine families could be differentiated. The performances of the RPA assays were validated using 37 milk powder samples, of which 16.2% (6/37) were suspected of being adulterated and 24.3% (9/37) were potentially at risk of being wrongly identified as adulteration. The effectiveness of the developed assays for crude DNA detection was also validated by a rapid nucleic acid extraction kit, and results showed that the presence of large amounts of protein and fat did not affect the qualitative results. Therefore, these assays could combine with the rapid nucleic acids extraction methods for being used in field detection.

Attenuated peripheral oxygen extraction and greater cardiac output in women with posttraumatic stress disorder during exercise.

Posttraumatic stress disorder (PTSD) is associated with an increased risk of developing cardiovascular disease, especially in women. Evidence indicates that men with PTSD exhibit lower maximal oxygen uptake (V̇o2max) relative to controls; however, whether V̇o2max is blunted in women with PTSD remains unknown. Furthermore, it is unclear what determinants (i.e., central and/or peripheral) of V̇o2max are impacted by PTSD. Therefore, we evaluated the central (i.e., cardiac output; Q̇c) and peripheral (i.e., arteriovenous oxygen difference) determinants of V̇o2max in women with PTSD; hypothesizing that V̇o2max would be lower in women with PTSD compared with women without PTSD (controls), primarily due to smaller increases in stroke volume (SV), and therefore Q̇c. Oxygen uptake (V̇o2), heart rate (HR), Q̇c, SV, and arteriovenous oxygen difference were measured in women with PTSD (n = 14; mean [SD]: 43 [11] yr,) and controls (n = 17; 45 [11] yr) at rest, and during an incremental maximal treadmill exercise test, and the Q̇c/V̇o2 slope was calculated. V̇o2max was not different between women with and without PTSD (24.3 [5.6] vs. 26.4 [5.0] mL/kg/min; P = 0.265). However, women with PTSD had higher Q̇c [P = 0.002; primarily due to greater SV (P = 0.069), not HR (P = 0.285)], and lower arteriovenous oxygen difference (P = 0.002) throughout exercise compared with controls. Furthermore, the Q̇c/V̇o2 slope was steeper in women with PTSD relative to controls (6.6 [1.4] vs. 5.7 [1.0] AU; P = 0.033). Following maximal exercise, women with PTSD exhibited slower HR recovery than controls (P = 0.046). Thus, despite attenuated peripheral oxygen extraction, V̇o2max is not reduced in women with PTSD, likely due to larger increases in Q̇c.NEW & NOTEWORTHY The current study indicates that V̇o2max is not different between women with and without PTSD; however, women with PTSD exhibit blunted peripheral extraction of oxygen, thus requiring an increase in Q̇c to meet metabolic demand during exercise. Furthermore, following exercise, women with PTSD demonstrate impaired autonomic cardiovascular control relative to sedentary controls. We interpret these data to indicate that women with PTSD demonstrate aberrant cardiovascular responses during and immediately following fatiguing exercise.

Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet ß cells in various mouse models of diabetes with distinct age of initiation.

During the pathogenesis of type 1 diabetes (T1D) and type 2 diabetes (T2D), pancreatic islets, especially the ß cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet (HFD) and streptozotocin (STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of islet ß cells. Cre-LoxP systems were used to generate islet cell type-specific (α, ß, or δ) green fluorescent protein (GFP)-labeled mice for genetic lineage tracing, thereinto ß-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing (scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled ß cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of ß cells and some of which transdifferentiated into a or δ cells in both youth- and adulthood-initiated mice while this phenomenon was barely observed in HFD models. ß cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into ß cells in STZ-treated mice (both youth- and adulthood-initiated). In addition to the re-dedifferentiation of ß cells, it is also highly likely that these "α or δ" cells transdifferentiated from pre-existing ß cells could also re-trans-differentiate into insulin-producing ß cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of ß cells. Our findings shed light on how islet ß cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.

Stress/cell death pathways, neuroinflammation, and neuropathic pain.

Neuropathic pain is a common and debilitating modality of chronic pain induced by a lesion or disease of the somatosensory nervous system. Albeit the elucidation of numerous pathophysiological mechanisms and the development of potential treatment compounds, safe and reliable therapies of neuropathic pain remain poor. Multiple stress/cell death pathways have been shown to be implicated in neuroinflammation during neuropathic pain. Here, we summarize the current knowledge of stress/cell death pathways and present an overview of the roles and molecular mechanisms of stress/cell death pathways in neuroinflammation during neuropathic pain, covering intrinsic and extrinsic apoptosis, autophagy, mitophagy, ferroptosis, pyroptosis, necroptosis, and phagoptosis. Small molecule compounds that modulate stress/cell death pathways in alleviating neuropathic pain are discussed mainly based on preclinical neuropathic pain models. These findings will contribute to in-depth understanding of the pathological processes during neuropathic pain as well as bridge the gap between basic and translational research to uncover new neuroprotective interventions.