Controversial role of γδ T cells in colorectal cancer.

Colorectal cancer (CRC) is the third most frequent type of cancer, and the second leading cause of cancer-related deaths worldwide. Current treatments for patients with CRC do not substantially improve the survival and quality of life of patients with advanced CRC, thus necessitating the development of new treatment strategies. The emergence of immunotherapy has revitalized the field, showing great potential in advanced CRC treatment. Owing to the ability of tumor cells to evade the immune system through major histocompatibility complex shedding and heterogeneous and low antigen spreading, only a few patients respond to immunotherapy. γδ T cells have heterogeneous structures and functions, and their key roles in immune regulation, tumor immunosurveillance, and specific primary immune responses have increasingly been recognized. γδ T cells recognize and kill CRC cells efficiently, thus inhibiting tumor progress through various mechanisms. However, γδ T cells can potentially promote tumor development and metastasis. Thus, given this dual role in prognosis, these cells can act as either a "friend" or "foe" of CRC. In this review, we explore the characteristics of γδ T cells and their functions in CRC, highlighting their application in immunotherapy.

Factors promoting and hindering resilience in youth with inflammatory bowel disease: A descriptive qualitative study.

AIM: To explore factors promoting and hindering resilience in youth with inflammatory bowel disease (IBD) based on Kumpfer's resilience framework. DESIGN: A descriptive qualitative study design with an interpretative approach was used. METHODS: Participants consisted of 10 youths with IBD from a tertiary hospital in Beijing (China) recruited using the purposive sampling method. Data were collected by semi-structured interviews from December 2020 to March 2021. The directed content analysis was performed for data analysis. RESULTS: Both promoting factors and hindering factors could be divided into personal factors and environmental factors. Thirteen themes were identified. The promoting factors included acceptance of illness, strict self-management, previous treatment experience, life goals, family support, medical support and peer encouragement. Stigma, lack of communication, negative cognition, societal incomprehension, economic pressure and academic and employment pressure were hindering factors. CONCLUSION: Health care professionals need to develop greater awareness of factors, stemming from both the individual and the outside world, that hinder or promote resilience in order to aid young patients with IBD. Building targeted nursing measures to excavate the internal positive quality of patients, provide external support and promote the development of resilience.

Molecular and epidemiological characterization of Staphylococcus aureus causing bovine mastitis in China.

BACKGROUND: Staphylococcus aureus is one of the most prevalent pathogens in bovine mastitis, which leads to substantial financial losses for the dairy industry. RESULTS: In this study, S. aureus (n = 72) was isolated from 18 dairy farms in 15 provinces across China in 2021. The identification of these isolates at the species level was achieved by employing 16S rRNA sequencing. An isothermal amplification method for auxiliary detection of S. aureus was established, which can be employed not only for laboratory detection but also for point-of-care testing (POCT). Molecular characteristics of S. aureus mastitis in Chinese dairy cows were determined through MLST and spa typing. Finally, methicillin-resistant Staphylococcus aureus (MRSA) and MRSA resistance genes were detected using MIC and PCR amplification techniques. 72 isolates were identified as 12 sequence types (STs) and 7 clonal complexes (CC). ST1/CC1 was the dominant prevalent accounting for 33.3 % of the total, and exhibiting a wide distribution range. In terms of spa types, t114 was the dominant type, accounting for 31.9 % of the total, followed by t529 as the second major type. Four S. aureus strains were classified as MRSA according to their levels of oxacillin resistance (MIC ≥4 µg/mL). Among these four MRSA strains, one of them was found to be mecA positive. However, the presence of drug-resistance genes mecA and mecC was not detected in the remaining three MRSA strains, indicating the possible existence of new resistance genes. CONCLUSIONS: Our study investigated the prevalence of S. aureus mastitis in dairy cows in China, while also examined the molecular characteristics and MRSA strains. This information will help with the clinical monitoring, prevention, and control of S. aureus mastitis in dairy cattle.

On the Relationship between MMA Levels in Blood Products and Donor Sex, Age, and Donation Frequency.

As the aging process accelerates, the age structure of blood donors turns to older and even aged groups. Methylmalonic acid (MMA), a byproduct of propionate metabolism, may be upregulated in the serum of older adults. As a mediator of chronic disease and tumor progression, the MMA content in blood products has become the focus of research. Absolute concentrations of MMA in blood products were determined based on the liquid chromatography-tandem mass spectrometry, so as to analyze how they were affected by donors' age, sex, and frequency of blood donation. The MMA content in leukocyte-depleted suspended red blood cell (lds-RBC) was significantly higher than that in fresh plasma (p<0.0001). The MMA content among five age groups showed no difference in either fresh plasma or lds-RBCs. The MMA content in fresh plasma was similar in the parameters of the sex, whereas that in lds-RBCs was higher in males than that in females (p=0.035). There were no significant differences in MMA content when it comes to different frequencies of blood donors in either fresh plasma or lds-RBCs. Additionally, there was no significant difference or clear trend in the rate of elevated plasma MMA levels among different sexes, age groups, and blood donation frequency groups. MMA in the blood products from donors in China does not compromise the safety of blood transfusions for cancer patients. Nevertheless, there is a need to focus on MMA levels in Chinese and to develop race-specific and age-specific normal reference ranges.

Novel Peptides from Sturgeon Ovarian Protein Hydrolysates Prevent Oxidative Stress-Induced Dysfunction in Osteoblast Cells: Purification, Identification, and Characterization.

This study aimed to explore antioxidant peptides derived from sturgeon (Acipenser schrenckii) ovaries that exhibit antiosteoporotic effects in oxidative-induced MC3T3-E1 cells. The F3-15 component obtained from sturgeon ovarian protein hydrolysates (SOPHs) via gel filtration and RP-HPLC significantly increased the cell survival rate (from 49.38 ± 2.88 to 76.26 ± 2.09%). Two putative antioxidant-acting peptides, FDWDRL (FL6) and FEGPPFKF (FF8), were screened from the F3-15 faction via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and through prediction by computer simulations. Molecular docking results indicated that the possible antioxidant mechanisms of FL6 and FF8 involved blocking the active site of human myeloperoxidase (hMPO). The in vitro tests showed that FL6 and FF8 were equally adept at reducing intracellular ROS levels, increasing the activity of antioxidant enzymes, and protecting cells from oxidative injuries by inhibiting the mitogen-activated protein kinase (MAPK) pathway and activating the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. Moreover, both peptides could increase differentiation and mineralization abilities in oxidatively damaged MC3T3-E1 cells. Furthermore, FF8 exhibited high resistance to pepsin and trypsin, showcasing potential for practical applications.

Prolyl hydroxylase inhibitor FG-4592 alleviates neuroinflammation via HIF-1/BNIP3 signaling in microglia.

BACKGROUND: Neuroinflammation is responsible for neuropsychiatric dysfunction following acute brain injury and neurodegenerative diseases. This study describes how a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor FG-4592 prevents the lipopolysaccharide (LPS)-induced acute neuroinflammation in microglia. METHODS: The distribution of FG-4592 in mouse brain tissues was determined by collision-induced dissociation tandem mass spectrometry. Microglial activation in the hippocampus was analyzed by immunofluorescence. Moreover, we determined the activation of HIF-1 and nuclear factor-κB (NF-κB) signaling pathways, proinflammatory responses using molecular biological techniques. Transcriptome sequencing and BNIP3 silencing were conducted to explore signaling pathway and molecular mechanisms underlying FG-4592 anti-inflammatory activity. RESULTS: FG-4592 was transported into the brain tissues and LPS increased its transportation. FG-4592 promoted the expression of HIF-1α and induced the downstream gene transcription in the hippocampus. Administration with FG-4592 significantly inhibited microglial hyperactivation and decreased proinflammatory cytokine levels following LPS treatment in the hippocampus. The LPS-induced inflammatory responses and the NF-κB signaling pathway were also downregulated by FG-4592 pretreatment in microglial cells. Mechanistically, Venn diagram analysis of transcriptomic changes of BV2 cells identified that BNIP3 was a shared and common differentially expressed gene among different treatment groups. FG-4592 markedly upregulated the protein levels of BNIP3 in microglia. Importantly, BNIP3 knockdown aggravated the LPS-stimulated inflammatory responses and partially reversed the protection of FG-4592 against microglial inflammatory signaling and microglial activation in the mouse hippocampus. CONCLUSIONS: FG-4592 alleviates neuroinflammation through facilitating microglial HIF-1/BNIP3 signaling pathway in mice. Targeting HIF-PHD/HIF-1/BNIP3 axis is a promising strategy for the development of anti-neuroinflammation drugs.

Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations.

Background: Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria® for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration. Methods: Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase. Results: Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel. Conclusion: Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.

Formononetin reverses Treg/Th17 imbalance in immune-mediated bone marrow failure mice by regulating the PI3K/Akt signaling pathway.

BACKGROUND: Severe aplastic anemia (SAA) is a syndrome of bone marrow failure which is life-threatening. Recent studies have demonstrated that CD4 + T cell subsets, including T regulatory (Treg) and T helper 17 (Th17) cells, play a pivotal role in the pathogenesis of SAA. Formononetin (FMN) is a natural compound extracted from the traditional Chinese medicine Huangqi, which has the ability to regulate the imbalance of Treg/Th17 cells in some inflammatory diseases. Nevertheless, the therapeutic effect of FMN in SAA has yet to be definitively established. Therefore, the objective of this research was to investigate the effect of FMN on SAA and elucidate its underlying mechanism. METHODS: In vivo experiments, the mice were divided into the following five groups: control, model, low-dose FMN, high-dose FMN, and positive control cyclosporine A group. The immune-mediated bone marrow failure (BMF) mouse model was established by the total body X-ray radiation and lymphocyte infusion. After 10 days of continuous administration of FMN, the numbers of Treg/Th17 cells in the bone marrow and spleen were assessed by flow cytometry. The protein expressions of PI3K/Akt pathway in the bone marrow and spleen was assessed by immunohistochemistry and western blotting. In vitro, the impact of FMN on the differentiation of naive CD4 + T cells into Treg cells was investigated by flow cytometry and ELISA. RESULTS: In comparison with the control group, the model group showed a reduction in bone marrow nucleated cells, a significant decrease in peripheral blood cells, and an altered CD8 + /CD4 + T cell ratio. These findings indicate the successful establishment of a mouse model of immune-mediated BMF. After FMN treatment, there were the increased levels of red blood cells and hemoglobin. In addition, FMN mitigated the bone marrow destruction and restored the CD8 + /CD4 + T cell ratio. Furthermore, in comparison with the control group, the model group showed the decreased levels of Treg cells and the increased levels of Th17 cells. After FMN treatment, there was a significantly increased number of Treg cells and a decreased number of Th17 cells. Additionally, FMN remarkably down-regulated the expression levels of PI3K and Akt proteins in immune-mediated BMF mice. CONCLUSIONS: FMN alleviates immune-mediated BMF by modulating the balance of Treg/Th17 cells through the PI3K/Akt signaling pathway.

Factors Influencing Breast Cancer Awareness in Rural Southwest China: A Cross-Sectional Study.

Background: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition. Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0. Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P<0.001) and decrease with increasing age (P<0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P<0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women's breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women's breast cancer awareness. Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.

Channel-forming discharge based on the extreme value identification of sediment-carrying capacity index.

Channel-forming discharge (Dcf) is an important parameter in river management and reservoir flood regulation. Applying the methods for calculating Dcf to reaches downstream reservoirs characterized by drastic changes in water and sediment conditions and long-term scouring status is difficult. Based on the riverbed-shaping principle of sediment-laden water flow, while simultaneously considering the active action of water flow and response of the riverbed, this study proposes a new method for calculating Dcf by identifying the extreme value of the suspended sediment-carrying capacity index. The application of this method to the middle and lower reaches of the Yangtze River showed that after the impoundment of the Three Gorges Reservoir, Dcf in this section was reduced by an amplitude between 2500 and 4700 m3/s. The results can be used to guide the operation of the Three Gorges Reservoir and the management of the middle and lower reaches of the Yangtze River, thus providing reference for other river channels downstream of the reservoir.

Exploring the Roles of Nurses in Medication Reconciliation for Older Adults at Hospital Discharge: A Narrative Approach.

Medication reconciliation (MR) is the process of comparing a patient's medication orders to all of the medications that the patient has been taking in order to identify and resolve medication discrepancies. It is an effective means of risk management to avoid medication errors (eg, omissions, duplication, dosage errors, or drug interactions). Some guidelines explicitly state that MR is a pharmacist-led transition of care; however, there is a shortage of qualified pharmacists to meet the increasing clinical needs, and clinical nurses' roles have not been clearly described. This paper aimed to enable nurses to gain confidence in contributing to MR at discharge and to make the industry aware of the potential risks if nurses do not actively intervene in this area. A narrative approach was used to introduce experiences in identifying discrepancies and medication errors through MR at discharge in a geriatric ward of an academic medical center hospital in China. The nurses' main roles in MR involve chasing, checking, and education. Clinical nurses, an untapped hospital resource, can actively engage in MR at discharge if they receive effective training and motivation. Multidisciplinary collaboration at discharge allowed many discrepancies to be reconciled before harming older patients. It is worth conducting further research in MR when discharging older adults, such as the cost-effectiveness of nurses' efforts, the value of electronic tools and the impact of MR-targeted education and training for nursing students and nursing staff.

Predictive Factors for the Formation of Viable Embryos in Subfertile Patients with Diminished Ovarian Reserve: A Clinical Prediction Study.

This study aims to construct and validate a nomogram for predicting blastocyst formation in patients with diminished ovarian reserve (DOR) during in vitro fertilization (IVF) procedures. A retrospective analysis was conducted on 445 DOR patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at the Reproductive Center of Yulin Maternal and Child Health Hospital from January 2019 to January 2023. A total of 1016 embryos were cultured for blastocyst formation, of which 487 were usable blastocysts and 529 did not form usable blastocysts. The embryos were randomly divided into a training set (711 embryos) and a validation set (305 embryos). Relevant factors were initially identified through univariate logistic regression analysis based on the training set, followed by multivariate logistic regression analysis to establish a nomogram model. The prediction model was then calibrated and validated. Multivariate stepwise forward logistic regression analysis showed that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 were independent predictors of blastocyst formation in DOR patients. The Hosmer-Lemeshow test indicated no statistical difference between the predicted probabilities of blastocyst formation and actual blastocyst formation (P > 0.05). These results suggest that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 are independent predictors of blastocyst formation in DOR patients. The clinical prediction nomogram constructed from these factors has good predictive value and clinical utility and can provide a basis for clinical prognosis, intervention, and the formulation of individualized medical plans.

Nanoparticles for the Treatment of Bone Metastasis in Breast Cancer: Recent Advances and Challenges.

Although the frequency of bone metastases from breast cancer has increased, effective treatment is lacking, prompting the development of nanomedicine, which involves the use of nanotechnology for disease diagnosis and treatment. Nanocarrier drug delivery systems offer several advantages over traditional drug delivery methods, such as higher reliability and biological activity, improved penetration and retention, and precise targeting and delivery. Various nanoparticles that can selectively target tumor cells without causing harm to healthy cells or organs have been synthesized. Recent advances in nanotechnology have enabled the diagnosis and prevention of metastatic diseases as well as the ability to deliver complex molecular "cargo" particles to metastatic regions. Nanoparticles can modulate systemic biodistribution and enable the targeted accumulation of therapeutic agents. Several delivery strategies are used to treat bone metastases, including untargeted delivery, bone-targeted delivery, and cancer cell-targeted delivery. Combining targeted agents with nanoparticles enhances the selective delivery of payloads to breast cancer bone metastatic lesions, providing multiple delivery advantages for treatment. In this review, we describe recent advances in nanoparticle development for treating breast cancer bone metastases.

A review of methods for assessment of cognitive function in high-altitude hypoxic environments.

Hypoxic environments like those present at high altitudes may negatively affect brain function. Varying levels of hypoxia, whether acute or chronic, are previously shown to impair cognitive function in humans. Assessment and prevention of such cognitive impairment require detection of cognitive changes and impairment using specific cognitive function assessment tools. This paper summarizes the findings of previous research, outlines the methods for cognitive function assessment used at a high altitude, elaborates the need to develop standardized and systematic cognitive function assessment tools for high-altitude hypoxia environments.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD-1 Therapy.

Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti-programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti-PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels and, when combined with dual CTLA-4/PD-1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+ T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient because CD8+ T cells from Cxcr3+/+ but not Cxcr3-/- mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti-CTLA-4 "priming" with chemotherapy followed by anti-PD-1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.

Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer.

ABSTRACT: Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Ferroptosis in cancer immunity and immunotherapy: Multifaceted interplay and clinical implications.

Ferroptosis is a type of cell death characterized by iron-dependent phospholipid peroxidation and reactive oxygen species overproduction. Ferroptosis induces immunogenic cell death and elicits anti-tumor immune responses, playing an important role in cancer immunotherapy. Ferroptosis suppression in cancer cells impairs its immunotherapeutic efficacy. To overcome this issue, ferroptosis inducers (FINs) have been combined with other cancer therapies to create an anti-tumor immune microenvironment. However, the ferroptosis-based crosstalk between immune and tumor cells is complex because oxidative products released by ferroptotic tumor cells impair the functions of anti-tumor immune cells, resulting in immunotherapeutic resistance. In the present article, we have reviewed ferroptosis in tumor and immune cells and summarized the crosstalk between ferroptotic tumor cells and the immune microenvironment. Based on the existing literature, we have further discussed future perspectives on opportunities for combining ferroptosis-targeted therapies with cancer immunotherapies.

Intermittent hypoxia training effectively protects against cognitive decline caused by acute hypoxia exposure.

Intermittent hypoxia training (IHT) is a promising approach that has been used to induce acclimatization to hypoxia and subsequently lower the risk of developing acute mountain sickness (AMS). However, the effects of IHT on cognitive and cerebrovascular function after acute hypoxia exposure have not been characterized. In the present study, we first confirmed that the simplified IHT paradigm was effective at relieving AMS at 4300 m. Second, we found that IHT improved participants' cognitive and neural alterations when they were exposed to hypoxia. Specifically, impaired working memory performance, decreased conflict control function, impaired cognitive control, and aggravated mental fatigue induced by acute hypoxia exposure were significantly alleviated in the IHT group. Furthermore, a reversal of brain swelling induced by acute hypoxia exposure was visualized in the IHT group using magnetic resonance imaging. An increase in cerebral blood flow (CBF) was observed in multiple brain regions of the IHT group after hypoxia exposure as compared with the control group. Based on these findings, the simplified IHT paradigm might facilitate hypoxia acclimatization, alleviate AMS symptoms, and increase CBF in multiple brain regions, thus ameliorating brain swelling and cognitive dysfunction.

Heat tolerance of a tropical-subtropical rainforest tree species Polyscias elegans: time-dependent dynamic responses of physiological thermostability and biochemistry.

Heat stress interrupts physiological thermostability and triggers biochemical responses that are essential for plant survival. However, there is limited knowledge on the speed plants adjust to heat in hours and days, and which adjustments are crucial. Tropical-subtropical rainforest tree species (Polyscias elegans) were heated at 40°C for 5 d, before returning to 25°C for 13 d of recovery. Leaf heat tolerance was quantified using the temperature at which minimal chl a fluorescence sharply rose (Tcrit ). Tcrit , metabolites, heat shock protein (HSP) abundance and membrane lipid fatty acid (FA) composition were quantified. Tcrit increased by 4°C (48-52°C) within 2 h of 40°C exposure, along with rapid accumulation of metabolites and HSPs. By contrast, it took > 2 d for FA composition to change. At least 2 d were required for Tcrit , HSP90, HSP70 and FAs to return to prestress levels. The results highlight the multi-faceted response of P. elegans to heat stress, and how this response varies over the scale of hours to days, culminating in an increased level of photosynthetic heat tolerance. These responses are important for survival of plants when confronted with heat waves amidst ongoing global climate change.