Climate velocities and species tracking in global mountain regions.

Mountain ranges contain high concentrations of endemic species and are indispensable refugia for lowland species that are facing anthropogenic climate change1,2. Forecasting biodiversity redistribution hinges on assessing whether species can track shifting isotherms as the climate warms3,4. However, a global analysis of the velocities of isotherm shifts along elevation gradients is hindered by the scarcity of weather stations in mountainous regions5. Here we address this issue by mapping the lapse rate of temperature (LRT) across mountain regions globally, both by using satellite data (SLRT) and by using the laws of thermodynamics to account for water vapour6 (that is, the moist adiabatic lapse rate (MALRT)). By dividing the rate of surface warming from 1971 to 2020 by either the SLRT or the MALRT, we provide maps of vertical isotherm shift velocities. We identify 17 mountain regions with exceptionally high vertical isotherm shift velocities (greater than 11.67 m per year for the SLRT; greater than 8.25 m per year for the MALRT), predominantly in dry areas but also in wet regions with shallow lapse rates; for example, northern Sumatra, the Brazilian highlands and southern Africa. By linking these velocities to the velocities of species range shifts, we report instances of close tracking in mountains with lower climate velocities. However, many species lag behind, suggesting that range shift dynamics would persist even if we managed to curb climate-change trajectories. Our findings are key for devising global conservation strategies, particularly in the 17 high-velocity mountain regions that we have identified.

Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history.

Hereditary tumor syndromes have garnered substantial attention due to their adverse effects on both the physical and psychological health of patients, as well as the elevated risk of transmission to subsequent generations. This has prompted a growing interest in exploring preimplantation genetic testing (PGT) as a treatment option to mitigate and eliminate these impacts. Several studies have demonstrated that de novo variants have become a great cause of many hereditary tumor syndromes, which introduce certain difficulties to PGT. In the absence of adequate genetic linkage information (parents and offspring), haplotype construction seems unrealizable. In the study, researchers used single sperm or affected embryos as proband to perform single-nucleotide polymorphism linkage analysis for cases with de novo variants. For complicated variants, the strategy that sperm combined with embryo detection will increase accuracy while avoiding the limitations and potential failures of using a single detection material. The study recruited 11 couples with male de novo carriers, including 3 tumor types and 4 genes. To date, 4 couples have been clinically confirmed as pregnant and three healthy babies have been born. The results of amniocentesis or umbilical cord blood verification were consistent with the results of PGT-M. The study aims to introduce the application of the PGT-M strategy in hereditary tumor syndromes.

A novel embryo biopsy morphological analysis and genetic integrality criterion system significantly improves the outcome of preimplantation genetic testing.

PURPOSE: While efforts have been made to establish blastocyst grading systems in the past decades, little research has examined the quality of biopsy specimens. This study is the first to correlate the morphology of biopsied trophectoderm (TE) cells to their quality and subsequent genetic testing results of preimplantation genetic testing (PGT), through an innovative Morphological Analysis and Genetic Integrality Criterion (MAGIC) system. METHODS: Biopsied TE cells were first evaluated according to the MAGIC procedure, followed by whole-genome amplification (WGA) and library construction, and then sequenced using the Illumina X Ten Platform. Copy number variation (CNV) and allele drop-out (ADO) rates as well as test failure rates were compared and analyzed. RESULTS: Our data explores the relationship between TE cell morphology and its quality and final genetic testing outcome, which is established based on the MAGIC system. MAGIC guarantees that only high- or good-quality TE cells are used for genetic testing to generate excellent data uniformity and lower ADO rates. Low-quality cells containing biopsied TE cell mass are responsible for the "background noise" of CNV analysis. CONCLUSION: The MAGIC application has effectively decreased the false-positive mosaicism, hence to ensure the stability and veracity of detection results, to avoid misdiagnoses, and to improve accuracy, as well as to avoid re-biopsy procedures. The study also contributes to understand how the IVF laboratory and the molecular biology laboratory depend on each other to achieve good-quality PGT results, which are clinically relevant for the patients.

Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations.

RESEARCH QUESTION: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next-generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)? DESIGN: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 × whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 × WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. RESULTS: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis. CONCLUSIONS: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.

Clinical application of an NGS-based method in the preimplantation genetic testing for Duchenne muscular dystrophy.

PURPOSE: To determine whether next-generation sequencing (NGS) could be used to directly detect different mutations of Duchenne muscular dystrophy (DMD) during preimplantation genetic testing (PGT). METHODS: From Sep. 2016 to Aug. 2018, a total of six couples participated in this study. Four cases carried DMD exon deletions and two carried exon duplications. Trophectoderm cells were biopsied at day 5 or 6 and NGS was used in the genetic testing of the biopsied cells after whole-genome amplification. We developed a new method-DIRected Embryonic Cell Testing of Exon Deletion/Duplication (DIRECTED) to directly detect the single-gene mutation by NGS. Linage analysis based on single-nucleotide polymorphism (SNP) was used to validate the results from DIRECTED. RESULTS: In the four deletion cases, DIRECTED was used to detect DMD exon deletion in 16 biopsied embryos. All DIRECTED results were consistent with linkage analysis, indicating this method was reliable in detecting deletions around 1 Mb. In the two cases carrying exon duplications, no blastocyst was obtained for biopsy. Nonetheless, preliminary experiment results suggested that DIRECTED could also be used for direct detection of exon duplications in embryos. CONCLUSIONS: Exon deletions or duplications in DMD of preimplantation embryos could be detected directly by NGS-based methods during PGT.

A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the development of renal cysts and progression to renal failure. Preimplantation genetic testing-monogenic disease (PGT-M) is an alternative option to obtain healthy babies. However, de novo PKD1 mutation of one of the spouses or the absence of a positive family history poses a serious challenge to PGT-M. Here, we described a comprehensive strategy which includes preimplantation genetic testing for aneuploidies (PGT-A) study and monogenic diagnosis study for ADPKD patients bearing de novo mutations. The innovation of our strategy is to use the gamete (polar body or single sperm) as proband for single-nucleotide polymorphism (SNP) linkage analysis to detect an embryo's carrier status. Nine ADPKD couples with either de novo mutation or without a positive family history were recruited and a total of 34 embryos from 13 PGT-M cycles were examined. Within these nine couples, two successfully delivered healthy babies had their genetic status confirmed by amniocentesis. This study provides a creative approach for embryo diagnosis of patients with de novo mutations or patients who lack essential family members for linkage analysis.

The Effects of Inter-Set Recovery Time on Explosive Power, Electromyography Activity, and Tissue Oxygenation during Plyometric Training.

Performing continuous sets to failure is fatiguing during the plyometric training. Cluster sets have been used to redistribute total rest time to create short frequent sets so that muscle fatigue can be avoided. The purpose of the study was to investigate the effects of inter-set recovery time on lower extremity explosive power, neuromuscular activity, and tissue oxygenation during plyometric exercise and recovery. An integrated assessment of explosive power, muscle electrical activity, and tissue oxygenation was adopted in the present study to help understand local muscle metabolism and fatigue during plyometric exercise and recovery. Ten university male basketball players participated in this study. Subjects performed 4 groups of exercise, each group comprised of 3 sets of jumps: 1, 2, 3, or 5 min. Surface electromyography (sEMG) signals were collected from 9 lower extremity muscles; near-infrared spectroscopy (NIRS) was recorded on vastus lateralis; mechanical data during plyometric exercise were collected from a force plate. No significant differences among sets and among groups were found regarding explosive power, jump height, EMG intensity, mean power frequency, the rate of tissue saturation index, and HbO2 changes between baseline and recovery. The current study has shown no muscular fatigue induced during the 4 groups of exercise. The results of this study may help inform recommendations concerning the recovery time during plyometric exercises at low loads (30% 1 RM).

scHaplotyper: haplotype construction and visualization for genetic diagnosis using single cell DNA sequencing data.

BACKGROUND: Haplotyping reveals chromosome blocks inherited from parents to in vitro fertilized (IVF) embryos in preimplantation genetic diagnosis (PGD), enabling the observation of the transmission of disease alleles between generations. However, the methods of haplotyping that are suitable for single cells are limited because a whole genome amplification (WGA) process is performed before sequencing or genotyping in PGD, and true haplotype profiles of embryos need to be constructed based on genotypes that can contain many WGA artifacts. RESULTS: Here, we offer scHaplotyper as a genetic diagnosis tool that reconstructs and visualizes the haplotype profiles of single cells based on the Hidden Markov Model (HMM). scHaplotyper can trace the origin of each haplotype block in the embryo, enabling the detection of carrier status of disease alleles in each embryo. We applied this method in PGD in two families affected with genetic disorders, and the result was the healthy live births of two children in the two families, demonstrating the clinical application of this method. CONCLUSION: Next generation sequencing (NGS) of preimplantation embryos enable genetic screening for families with genetic disorders, avoiding the birth of affected babies. With the validation and successful clinical application, we showed that scHaplotyper is a convenient and accurate method to screen out embryos. More patients with genetic disorder will benefit from the genetic diagnosis of embryos. The source code of scHaplotyper is available at GitHub repository: https://github.com/yzqheart/scHaplotyper.

Trio-whole-exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations.

Whole-exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio-WES, we identified 32 disease-associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease-associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.

A strategy using SNP linkage analysis for monogenic diseases PGD combined with HLA typing.

Preimplantation genetic diagnosis (PGD) of genetic diseases, combined with human leukocyte antigen (HLA) typing (PGD-HLA), is a useful technique to have healthy offspring that are compatible with a sibling for hematopoietic stem cells transplantation (HSCT) to treat their genetic diseases. Here, we report a new strategy using single nucleotide polymorphism (SNP) linkage analysis for monogenic disease PGD combined with HLA typing, to simultaneously obtain the information of chromosomal aneuploidy, target mutations and HLA typing through a single low-depth next generation sequencing (NGS) procedure. In this study, five couples with probands underwent SNP linkage analysis for PGD-HLA typing were recruited. Within these five couples, two couples fortunately harvested four unaffected and HLA matched embryos with their siblings. After embryo transfer, two healthy neonates were born successfully. Subsequently, cord blood hematopoietic stem cells obtained from these two neonates were collected and frozen for treating their sick siblings. This novel strategy could provide abundant and specific SNPs for each family, therefore linkage information adjacent and even within HLA clusters were apparent. This study offers a highly flexible and precise method which could eliminate misdiagnosis caused by chromosomal recombination of the HLA gene, thus potentially benefit the success rate of HSCT.

Novel PGD strategy based on single sperm linkage analysis for carriers of single gene pathogenic variant and chromosome reciprocal translocation.

PURPOSE: Preimplantation genetic diagnosis (PGD) analysis can be challenging for couples who carry more than one genetic condition. In this study, we describe a new PGD strategy to select which embryo(s) to transfer for two clinically challenging cases. Both cases lack essential family members for linkage analysis including de novo mutation combined with reciprocal translocation. METHODS: Diverging from conventional method, we performed direct point mutation detection, quantitative analysis of gene copy number, combined with linkage analysis assisted by SNP information from single sperm (or polar bodies), thus establishing an all-in-one protocol for single embryonic cell preimplantation diagnosis for two co-existing genetic conditions (monogenic disease and chromosomal abnormality) on the NGS-based platform. RESULTS: Using this newly developed method, 15 embryos from two cases were screened, and two embryos were determined as free of the monogenic disease and specific chromosomal abnormalities created by the prospective father's reciprocal translocations. CONCLUSION: This novel PGD strategy could effectively select unaffected embryo(s) for couples affected with or carrying a monogenetic disease and a reciprocal chromosome translocation concurrently.

Standard early rehabilitation and lower limb transcutaneous nerve or neuromuscular electrical stimulation in acute stroke patients: a randomized controlled pilot study.

OBJECTIVE: We investigated adding lower limb transcutaneous nerve stimulation or neuromuscular electrical stimulation to standard early rehabilitation in acute stroke patients. DESIGN: An assessor-blinded, randomized controlled pilot study. SETTING: A medical stroke center. SUBJECTS: First-stroke patients aged 20-80 years admitted to the stroke center within 24 hours post stroke. INTERVENTIONS: A total of 42 participants were randomly assigned to groups: transcutaneous nerve stimulation + standard early rehabilitation, neuromuscular electrical stimulation + standard early rehabilitation, or standard early rehabilitation-only. Transcutaneous nerve or neuromuscular electrical stimulation was delivered to the affected tibialis anterior and quadriceps muscles for 30 minutes a day, five days per week for two weeks. MAIN MEASURES: The Postural Assessment Scale for Stroke Patients, the Functional Independence Measure, and three mobility milestones, namely, sitting for >five minutes, standing for >one minute, and walking ⩾50 m, were evaluated, respectively, at baseline, at the two-week post-intervention, and at two-week follow-up. RESULTS: Significant differences existed in the Postural Assessment Scale for Stroke Patients scores between the transcutaneous nerve stimulation and standard early rehabilitation-only groups measured at two-weeks post-intervention (mean (SD) = 31.38 (5.39) and 18.00 (8.65), respectively) and at the two-week follow-up (34.08 (2.69) and 26.14 (7.77), respectively). A higher proportion of participants could walk ⩾50 m independently in the transcutaneous nerve stimulation group than in the standard early rehabilitation-only group at the two-week post-intervention (P = 0.013) and two-week follow-up (P = 0.01) marks. CONCLUSION: Two weeks of transcutaneous nerve stimulation added to standard early rehabilitation improved postural stability and walking in acute stroke patients.

Reliability of lower extremity muscle strength measurements with handheld dynamometry in stroke patients during the acute phase: a pilot reliability study.

[Purpose] No literature has described a suitable method for measuring muscle strength in a supine position during acute phase after stroke. This study investigated the feasibility and reliability of using a commercial handheld dynamometer to measure the muscle strengths of the hip flexor, knee extensor, and dorsiflexor in the supine position with a modified method for patients at a stroke intensive care center within 7 days of stroke onset. [Subjects and Methods] Fifteen persons with acute stroke participated in this cross-sectional study. For each patient, the muscle strengths of the hip flexors, knee extensors, and dorsiflexors were measured twice by two testers on the same day. Each patient was re-tested at the same time of day one day later. Inter-rater and test-retest reliability were then determined by the intraclass correlation coefficients (ICCs). [Results] For the three muscle groups, the inter-rater reliability ICCs were all 0.99 and the test-retest reliability ICCs were greater than 0.85. The investigated method thus has good inter-rater reliability and high agreement between the test-retest measurements, with acceptable measurement errors. [Conclusion] The modified method using a handheld dynamometer to test the muscle strength of acute stroke patients is a feasible and reliable method for clinical use.

[Experimental study on anti-tumor effect of xihuang pill and its immune clearance function].

OBJECTIVE: To discuss the anti-tumor effect of Xihuang pill on tumor-bearing rats and its effect on the immune clearance function of tumor-bearing organisms. METHOD: Walker256 tumor cells were adopted to establish the tumor-bearing rat model. The rats were randomly divided into five groups: the normal control group, the model control group, the lentinan group and Xihuang pill low dose, middle dose and high dose groups, with 10 rats in each group, and continuously treated and given drugs for 14 d after modeling. Blood and tumors were collected from abdominal aorta to calculate the tumor inhibition rate. The content of CD3+, CD4+, CD8+ T cells and adhesion molecule B7-1 (CD80) in peripheral blood were detected by flow cytometry (FCM). The expressions of IL-2 and IFN-gamma in were determined by ELISA. RESULT: The tumor inhibition rate of the Xihuang pill high dose group was 33. 1 percent. Compared with the model group, the Xihuang pill large dose group showed significantly low IL-2, IFN-gamma, CD3+, CD4+, B7-1 in peripheral blood, with statistical significance in their differences (P < 0.05). CONCLUSION: Xihuang pill could show its anti-tumor effect by enhancing the immune clearance function and increasing IL-2, IFN-gamma, CD3+ T, CD4+ T, B7-1 in peripheral blood.

Impact of Early Mobilization on Patients With Acute Ischemic Stroke Treated With Thrombolysis or Thrombectomy: A Randomized Controlled Trial.

BACKGROUND: Early mobilization (EM) within 24 to 72 hours post-stroke may improve patients' performance and ability. However, after intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), the increased risk of hemorrhagic complications impacts the implementation of early out-of-bed mobilization. Few studies have investigated EM after IVT or MT for acute ischemic stroke (AIS), and its impact in these patients is unknown. OBJECTIVE: To investigate the effect of EM on AIS treated with IVT or MT.|. METHODS: We recruited 122 patients with first AIS; 60 patients were treated with IVT, and 62 patients were treated with MT. For each IVT and MT cohort, the control groups received standard early rehabilitation, and the intervention groups received an EM protocol. The training lasted 30 minutes/day, 5 days/week until discharge. MAIN OUTCOMES MEASURES: The effectiveness of the interventions was evaluated using the motor domain of the Functional Independence Measure (FIM-motor) and the Postural Assessment Scale for Stroke Patients (PASS) at baseline, 2-week, 4-week, and 3-month post-stroke, the Functional Ambulation Category 2-week post-stroke, and the total length of stay at the stroke center. RESULTS: Both IVT and MT treatment groups showed improved FIM-motor and PASS scores over time; however, only the IVT EM group had significantly improved FIM-motor performance within 1 month after stroke than the control group. Conclusion. An EM protocol with the same intervention time and session frequency per day as in the standard care protocol was effective in improving the functional ability of stroke patients after IVT.

Simultaneous production of biosurfactant and extracellular unspecific peroxygenases by Moesziomyces aphidis XM01 enables an efficient strategy for crude oil degradation.

Crude oil is a hazardous pollutant that poses significant and lasting harm to human health and ecosystems. In this study, Moesziomyces aphidis XM01, a biosurfactant mannosylerythritol lipids (MELs)-producing yeast, was utilized for crude oil degradation. Unlike most microorganisms relying on cytochrome P450, XM01 employed two extracellular unspecific peroxygenases, MaUPO.1 and MaUPO.2, with preference for polycyclic aromatic hydrocarbons (PAHs) and n-alkanes respectively, thus facilitating efficient crude oil degradation. The MELs produced by XM01 exhibited a significant emulsification activity of 65.9% for crude oil and were consequently supplemented in an "exogenous MELs addition" strategy to boost crude oil degradation, resulting in an optimal degradation ratio of 72.3%. Furthermore, a new and simple "pre-MELs production" strategy was implemented, achieving a maximum degradation ratio of 95.9%. During this process, the synergistic up-regulation of MaUPO.1, MaUPO.1 and the key MELs synthesis genes contributed to the efficient degradation of crude oil. Additionally, the phylogenetic and geographic distribution analysis of MaUPO.1 and MaUPO.1 revealed their wide occurrence among fungi in Basidiomycota and Ascomycota, with high transcription levels across global ocean, highlighting their important role in biodegradation of crude oil. In conclusion, M. aphidis XM01 emerges as a novel yeast for efficient and eco-friendly crude oil degradation.

Efficacy and safety of different doses of epidural morphine coadministered with low-concentration ropivacaine after cesarean section: A retrospective cohort study.

Objective: The optimal dose of epidural morphine after cesarean section (CS) still remains unknown when combined with low-concentration ropivacaine based on a continuous basal infusion (CBI) mode. The aim of this study was to assess the impact of different dose of epidural morphine plus ropivacaine on maternal outcomes. Materials and methods: Data of parturients who received epidural analgesia for CS at a teaching hospital from March 2021 to June 2022 were retrospectively collected. Parturients were divided into two groups (RM3 group and RM6 group) according to different medication regimens of morphine. The implementation of epidural analgesia was performed with 3 mg morphine in RM3 group and 6 mg morphine in RM6 group in combination with 0.1% ropivacaine via a CBI pump. The primary outcomes included pain intensity at rest and movement and the incidence of urinary retention and pruritus within postoperative 48 h. The secondary outcomes included the incidence and severity of postoperative nausea and vomiting (PONV) and pruritus, the rate of rescue analgesia and grading of motor Block. Results: Totally, 531 parturients were eligible for the final analysis, with 428 and 103 parturients in the RM3 group and RM6 group, respectively. There were no statistically significant differences in the visual analogue scores (VAS) at rest and movement within postoperative 48 h between the two groups (all p > 0.05). Compared with the RM6 group, the incidence of urinary retention was lower in the RM3 group within 48 h after CS (4.0% vs. 8.7%, p = 0.044). No significant difference was found in the incidence and severity of PONV and pruritus, the rate of rescue analgesia and grading of motor block between RM3 and RM6 groups. Conclusion: Epidural 3 mg morphine plus 0.1% ropivacaine in a CBI mode can provide equal efficacy and have lower incidence of urinary retention compared with 6 mg morphine after CS.

Precisely Amplifying Intracellular Oxidative Storm by Metal-Organic Coordination Polymers to Augment Anticancer Immunity.

Oxidative stress accompanying the reactive oxygen species (ROS) burst governs immunocyte infiltration, activation, and differentiation in tumor microenvironments and thus can elicit robust antitumor immunity. Here, we identify a photoactive metal-organic coordination polymer (MOCP), composed of an organometallic core formed by cytotoxic mitoxantrone (MTX) acylates and photosensitive Ru(BIQ)-HDBB [BIQ = 2,2'-biquinoline, HDBB = 4,4'-di(4-benzoato)-2,2'-bipyridine] linked by Fe(II) ions via coordinate covalent bonds and an amphipathic shell encapsulating cholesterol-modified siRNA against GPX4 (siGPX4) via hydrophobic force, to precisely amplify intracellular oxidative storm. MOCPs simultaneously encapsulated MTX, Ru, and siGPX4 with efficiencies >98% and loaded Fe with efficiencies of ∼0.49%. With longer blood circulation and higher tumor accumulation, MOCPs with a 670 nm LED irradiation generate abundant ROS to induce biomembrane dysfunction and subsequently contribute to ferroptotic and immunogenic cell death, which drive tumor-associated antigen-specific immunity. MTX analogs contributed to Type I immunogenic cell death (ICD), while oxidative storm served as a damager for endo/lysosomal escape, an initiator for ferroptosis, and an inducer for type II ICD. Moreover, the blockade of CD73 that reduces extoATP catabolism unleashes immunosuppression, finally enhancing antitumor immune stimulation of MOCPs to promote orthotopic mammary cancer regression and prevent postoperative advanced cancer from recurrence and metastasis. MOCPs by exposing sufficient antigenicity thus provide a platform to synergize immune checkpoint inhibitors for the treatment of immunologically cold tumors.

Differences in muscle coordination between older men and women during brisk walking.

Brisk walking is a highly recommended physical activity for healthy community-dwelling older adults. The objective of this study was to examine through principal component analysis (PCA) how muscle coordination differs between older women and men during brisk walking. Thirty-five healthy older adults (65.2 ± 3.0 years old, 18 females, and 17 males) participated in the study. Eight surface electromyographic electrodes were used to record lower extremity muscle activities, and four inertial measurement unit sensors to monitor hip, knee, and ankle motion. Energy expenditure and heart rate were also measured during brisk walking. The effects of a person's sex on muscle coordination were identified through wavelet and PCA analysis of the sEMG signals. The results of energy expenditure and heart rate confirmed that brisk walking exercise is beneficial for older adults. PCA analysis showed that muscle coordination patterns differ between older women and men: during the stance phase a greater co-contraction of tibialis anterior and soleus in the men, and a greater activation of the quadriceps muscles during the loading-response phase in the women. The wavelet and PCA analyses facilitated a quantitative appraisal of sex-specific differences in the muscle coordination patterns of older men and women during brisk walking.

Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study.

Introduction: Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS). Methods: Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory. Results: During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest. Discussion: These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.