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Stroke is associated with diaphragmatic weakness and impaired respiratory function as well as balance impairment. The role of inspiratory muscle training (IMT) on improvement of respiratory muscle strength in people after stroke has been reported. However, the training intensity associated with optimal diaphragm recruitment and the relationship between the effect of IMT and other functions in this population remains uncertain. This randomized controlled trial (RCT) aims to explore the effects of a 4-week IMT program with training intensity at 50% maximum inspiratory pressure (MIP) (previously shown to be associated with maximal diaphragm contraction), on respiratory function, balance control, exercise capacity and quality of life (QOL) in people after stroke. This is a patient- and assessor-blinded RCT. Eligible participants will be randomly allocated to the targeted-IMT group (with 50% MIP as the training intensity) or sham-IMT group (with 10% MIP as the training intensity). Both groups will also receive the same standardised hospital-based physical-rehabilitation protocol. All interventions will be implemented 5 days/week for 4 weeks. The primary outcome is the change of diaphragmatic thickness. Secondary outcomes are spirometry respiratory function, balance control, exercise capacity and QOL. Assessment will be conducted at baseline, post-intervention, and at 12th week follow-up. Data will be primarily analysed using repeated-measures ANOVA α=0.05. Results of this study will primarily inform the effect of IMT on lung function, balance control, exercise capacity and QOL in addition to physical rehabilitation, further the interplay between the change in diaphragm thickness, balance and QOL will be analysed in detail.

The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT 50 ) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3–5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT 50 titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed. Serum neutralizing antibody titers against the SARS-CoV-2 Omicron variant markedly increase after a third dose of BNT162b2 vaccine in individuals who previously received either two doses of the BNT162b2 vaccine or two doses of the CoronaVac vaccine.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January–July 2022. We estimated that Omicron infected 45% (41–48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34–64%) and 69% (46–98%) for three and four doses of BNT162b2, respectively; VE of 30% (1–66%) and 56% (6–97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7–41%) and 35% (10–71%) for three and four doses of BNT162b2, and to 6% (0–29%) and 11% (0–54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE. An analysis of sera samples collected between January and July of 2022 in Hong Kong shows that the effectiveness of both the BNT162b2 and CoronaVac COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 variant infection waned rapidly after the third and fourth doses.

Purpose Remediation of metal contaminated soil with biochar is attracting extensive interest in recent years. Understanding the significance of variable biochar properties and soil types helps elucidating the meticulous roles of biochar in immobilizing/mobilizing metals/metalloids in contaminated soils. Materials and methods Six biochars were produced from widely available agricultural wastes (i.e., soybean stover, peanut shells and pine needles) at two pyrolysis temperatures of 300 and 700 °C, respectively. The Pb-, Cu-, and Sb-contaminated shooting range soils and Pb-, Zn-, and As-contaminated agricultural soils were amended with the produced biochars. The mobility of metals/metalloids was assessed by the standard batch leaching test, principal component analysis and speciation modeling. Results and discussion The changes in soil properties were correlated to feedstock types and pyrolysis temperatures of biochars based on the principal component analysis. Biochars produced at 300 °C were more efficient in decreasing Pb and Cu mobility (>93 %) in alkaline shooting range soil via surface complexation with carboxyl groups and Fe-/Al-minerals of biochars as well as metal-phosphates precipitation. By contrast, biochars produced at 700 °C outperformed their counterparts in decreasing Pb and Zn mobility (100 %) in acidic agricultural soil by metal-hydroxides precipitation due to biochar-induced pH increase. However, Sb and As mobility in both soils was unfavorably increased by biochar amendment, possibly due to the enhanced electrostatic repulsion and competition with phosphate. Conclusions It is noteworthy that the application of biochars is not equally effective in immobilizing metals or mobilizing metalloids in different soils. We should apply biochar to multi-metal contaminated soil with great caution and tailor biochar production for achieving desired outcome and avoiding adverse impact on soil ecosystem.

This study reports the concomitant contraction pattern of the diaphragm and sternocleidomastoid (SCM) muscles at various inspiratory pressure loads in patients after stroke. Thirty-six participants (stroke duration: 3.6 ± 2.9 months) performed in random order, sets of 10 breaths at inspiratory loads of 30, 40, 50, 60, 70 and 80%, maximum inspiratory pressure (MIP). Bilateral muscle activity of the SCMs and diaphragm thickness were recorded simultaneously using surface electromyography (sEMG) and ultrasonography, respectively. Diaphragmatic thickness was significantly lower on the hemiplegic side compared to the non-affected side. The magnitude of diaphragmatic contraction, reflected by the calculated thickening fraction (DTf) for both hemidiaphragms, increased with inspiratory load and peaked at 50% MIP, but then decreased with any further increase in inspiratory pressure. SCM recruitment continued to increase bilaterally with increasing inspiratory pressure and was highest at 80% MIP, with recruitment activity significantly higher on the hemiplegic side compared to the non-affected side. Our results suggest that inspiratory load demands above 50%MIP are primarily met by increased SCM activity without any increase in diaphragmatic contraction. Adopting training intensities greater than 50%MIP in clinical inspiratory muscle training (IMT) programs needs to be re-considered.

Biological microswimmers can coordinate their motions to exploit their fluid environment—and each other—to achieve global advantages in their locomotory performance. These cooperative locomotion require delicate adjustments of both individual swimming gaits and spatial arrangements of the swimmers. Here we probe the emergence of such cooperative behaviors among artificial microswimmers endowed with artificial intelligence. We present the first use of a deep reinforcement learning approach to empower the cooperative locomotion of a pair of reconfigurable microswimmers. The AI-advised cooperative policy comprises two stages: an approach stage where the swimmers get in close proximity to fully exploit hydrodynamic interactions, followed a synchronization stage where the swimmers synchronize their locomotory gaits to maximize their overall net propulsion. The synchronized motions allow the swimmer pair to move together coherently with an enhanced locomotion performance unattainable by a single swimmer alone. Our work constitutes a first step toward uncovering intriguing cooperative behaviors of smart artificial microswimmers, demonstrating the vast potential of reinforcement learning towards intelligent autonomous manipulations of multiple microswimmers for their future biomedical and environmental applications.

Accurate prediction of aerobic capacity is necessary to guide appropriate exercise prescription. It is common to use 6-minute walk distance (6MWD) to predict peak oxygen uptake (VO 2peak ) in the clinical environment. The aim of this study was to determine whether prediction of VO 2peak can be improved by the inclusion of cardiovascular indices derived by impedance cardiography (ICG) during the 6MWT. A total of 62 healthy university students aged 21±1 years completed in separate days, a cardiopulmonary exercise test (CPET) and two 6MWTs (30 min apart), during which heart rate (HR), stroke volume (SV) and cardiac output (CO) were measured by ICG (PhysioFlow ® PF07 Enduro TM ). The CPET was conducted with the Ergoselect 200 Ergoline and oxygen consumption measured by a MasterScreen TM CPX breath-by-breath metabolic cart. Multiple regression analyses were conducted to generate VO 2peak prediction equations using 6MWD with, or without the cardiovascular indices recorded at the end of the best performed 6MWT as predictor variables. The mean peak HR (bpm), SV (ml) and CO (L/min) recorded during 6MWT were 156±18, 95.6±9, 15±2.8 and during CPET were 176±16, 91.3±8, 16.2±2.7, respectively. Analyses revealed the following VO 2peak prediction equation: VO 2peak = 100.297+(0.019x6MWD)+(-0.598xHR 6MWT )+(-1.236xSV 6MWT ) + (8.671 x CO 6MWT ). This equation has a squared multiple correlation ( R 2 ) of 0.866, standard error of the estimate (SEE) of 2.28 mL/kg/min and SEE:VO 2peak (SEE%) of 7.2%. Cross-validation of equation stability using predicted residual sum of squares (PRESS) statistics showed a R 2 ( R p 2 ), SEE (SEE p ) and SEE p % of 0.842, 2.38 mL/kg/min and 7.6% respectively. The minimal shrinkage of R 2 implied regression model stability. Correlation between measured and predicted VO 2peak using this equation was strong (r = 0.931, p<0.001). When 6MWD alone was used as the predictor for VO 2peak , the generated equation had a lower R 2 (0.549), and a higher SEE (4.08 mL/kg/min) and SEE% (12.9%). This is the first study which included cardiac indices during a 6MWT as variables for VO 2peak prediction. Our results suggest that inclusion of cardiac indices measured during the 6MWT more accurately predicts VO 2peak than using 6MWD data alone.

Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase that relays nutrient availability signals to control numerous cellular functions including autophagy, a process of cellular self-eating activated by nutrient depletion. Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with pharmacologically desirable properties. Using an automated cell-based assay, we screened a collection of >3,500 chemicals and identified three approved drugs (perhexiline, niclosamide, amiodarone) and one pharmacological reagent (rottlerin) capable of rapidly increasing autophagosome content. Biochemical assays showed that the four compounds stimulate autophagy and inhibit mTORC1 signaling in cells maintained in nutrient-rich conditions. The compounds did not inhibit mTORC2, which also contains mTOR as a catalytic subunit, suggesting that they do not inhibit mTOR catalytic activity but rather inhibit signaling to mTORC1. mTORC1 inhibition and autophagosome accumulation induced by perhexiline, niclosamide or rottlerin were rapidly reversed upon drug withdrawal whereas amiodarone inhibited mTORC1 essentially irreversibly. TSC2, a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone. Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2, an upstream regulator of mTORC1. By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. The observation that drugs already approved for human use can reversibly inhibit mTORC1 and stimulate autophagy should greatly facilitate the preclinical and clinical testing of mTORC1 inhibition for indications such as tuberous sclerosis, diabetes, cardiovascular disease and cancer.

The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type–specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions.

Background There is limited evidence to support the use of vestibular rehabilitation therapy (VRT) on improving balance and gait in patients after stroke. This systematic review aimed to evaluate the effects of VRT in addition to usual rehabilitation compared with usual rehabilitation on improving balance and gait for patients after stroke. Methods This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement guidelines. Ten electronic databases were searched up to 1 June 2023 without restrictions in language and publication status. The PEDro scale and the Grading of Recommendations Assessment Development, and Evaluation were used to evaluate the risk of bias and the certainty of evidence. The meta-analysis was conducted with Review Manager 5.3. Results Fifteen randomised controlled trials with 769 participants were included. PEDro scale was used to assess the risk of bias with a mean score of 5.9 (0.7). VRT was effective in improving balance for patients after stroke (SMD = 0.59, 95% CI (0.40, 0.78), p  < 0.00001), particularly for patients after stroke that occurred within 6 months (SMD = 0.56, 95% CI (0.33, 0.79), p  < 0.00001) with moderate certainty of evidence. Subgroup analysis showed that VRT provided as gaze stability exercises combined with swivel chair training (SMD = 0.85, 95% CI (0.48, 1.22), p  < 0.00001) and head movements (SMD = 0.75, 95% CI (0.43, 1.07), p  < 0.00001) could significantly improve balance. Four-week VRT had better effect on balance improvement (SMD = 0.64, 95% CI (0.40, 0.89), p  < 0.00001) than the less than 4-week VRT. The pooled mean difference of values of Timed Up-and-Go test showed that VRT could significantly improve gait function for patients after stroke (MD =  −4.32, 95% CI (−6.65, −1.99), p  = 0.0003), particularly for patients after stroke that occurred within 6 months (MD =  −3.92, 95% CI (−6.83, −1.00), p  = 0.008) with moderate certainty of evidence. Conclusions There is moderate certainty of evidence supporting the positive effect of VRT in improving balance and gait of patients after stroke. Trial registration PROSPERO CRD42023434304