Disruption of the rice 4-DEOXYOROBANCHOL HYDROXYLASE unravels specific functions of canonical strigolactones.

Strigolactones (SLs) regulate many developmental processes, including shoot-branching/tillering, and mediate rhizospheric interactions. SLs originate from carlactone (CL) and are structurally diverse, divided into a canonical and a noncanonical subfamily. Rice contains two canonical SLs, 4-deoxyorobanchol (4DO) and orobanchol (Oro), which are common in different plant species. The cytochrome P450 OsMAX1-900 forms 4DO from CL through repeated oxygenation and ring closure, while the homologous enzyme OsMAX1-1400 hydroxylates 4DO into Oro. To better understand the biological function of 4DO and Oro, we generated CRISPR/Cas9 mutants disrupted in OsMAX1-1400 or in both OsMAX1-900 and OsMAX1-1400. The loss of OsMAX1-1400 activity led to a complete lack of Oro and an accumulation of its precursor 4DO. Moreover, Os1400 mutants showed shorter plant height, panicle and panicle base length, but no tillering phenotype. Hormone quantification and transcriptome analysis of Os1400 mutants revealed elevated auxin levels and changes in the expression of auxin-related, as well as of SL biosynthetic genes. Interestingly, the Os900/1400 double mutant lacking both Oro and 4DO did not show the observed Os1400 architectural phenotypes, indicating their being a result of 4DO accumulation. Treatment of wild-type plants with 4DO confirmed this assumption. A comparison of the Striga seed germinating activity and the mycorrhization of Os900, Os900/1400, and Os1400 loss-of-function mutants demonstrated that the germination activity positively correlates with 4DO content while disrupting OsMAX1-1400 has a negative impact on mycorrhizal symbiosis. Taken together, our paper deciphers the biological function of canonical SLs in rice and reveals their particular contributions to establishing architecture and rhizospheric communications.

Abscisic acid inhibits germination of Striga seeds and is released by them likely as a rhizospheric signal supporting host infestation.

Seeds of the root parasitic plant Striga hermonthica undergo a conditioning process under humid and warm environments before germinating in response to host-released stimulants, particularly strigolactones (SLs). The plant hormone abscisic acid (ABA) regulates different growth and developmental processes, and stress response; however, its role during Striga seed germination and early interactions with host plants is under-investigated. Here, we show that ABA inhibited Striga seed germination and that hindering its biosynthesis induced conditioning and germination in unconditioned seeds, which was significantly enhanced by treatment with the SL analog rac-GR24. However, the inhibitory effect of ABA remarkably decreased during conditioning, confirming the loss of sensitivity towards ABA in later developmental stages. ABA measurement showed a substantial reduction of its content during the early conditioning stage and a significant increase upon rac-GR24-triggered germination. We observed this increase also in released seed exudates, which was further confirmed by using the Arabidopsis ABA-reporter GUS marker line. Seed exudates of germinated seeds, containing elevated levels of ABA, impaired the germination of surrounding Striga seeds in vitro and promoted root growth of a rice host towards germinated Striga seeds. Application of ABA as a positive control caused similar effects, indicating its function in Striga/Striga and Striga/host communications. In summary, we show that ABA is an essential player during seed dormancy and germination processes in Striga and acts as a rhizospheric signal likely to support host infestation.

Oxidative stress induces chromosomal instability through replication stress in fibroblasts from aged mice.

Chromosomal aneuploidy has been associated with aging. However, whether and how chromosomal instability (CIN), a condition frequently seen in cancer cells in which chromosome missegregation occurs at a high rate, is associated with aging is not fully understood. Here, we found that primary fibroblasts isolated from aged mice (24 months old) exhibit an increased level of chromosome missegregation and micronucleation compared with that from young mice (2 months old), concomitant with an increased rate of aneuploid cells, suggesting the emergence of CIN. Reactive oxygen species were increased in fibroblasts from aged mice, which was accompanied with mitochondrial functional decline, indicating that they are under oxidative stress. Intriguingly, antioxidant treatments reduced chromosome missegregation and micronucleation rates in cells from aged mice, suggesting a link between oxidative stress and CIN. As a cause of CIN, we found that cells from aged mice are under replication stress, which was ameliorated by antioxidant treatments. Microtubule stabilization is a potential cause of CIN promoted by replication stress. Our data demonstrate the emergence of CIN with age, and suggest an unprecedented link between oxidative stress and CIN in aging.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Mixed active metabolites of the SNP-6 series of novel compounds mitigate metabolic dysfunction-associated steatohepatitis and fibrosis: promising results from pre-clinical and clinical trials.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern with no effective pharmacological treatments. SNP-630, a newly developed synthetic molecule with multiple mechanisms of action, and a mixture of two of its active metabolites (SNP-630-MS) inhibit CYP2E1 expression to prevent reactive oxygen species generation, thereby reducing the accumulation of hepatic triglycerides and lowering chemokine levels. This study investigated the SNP-630's potential to alleviate the liver injury in MASH and its efficacy in both a mouse model and patients with MASH to identify a drug candidate that targets multiple pathways implicated in MASH. METHODS: SNP-630 and SNP-630-MS were separately administered to the MASH mouse model. The tolerability, safety, and efficacy of SNP-630-MS were also evaluated in 35 patients with MASH. The primary endpoint of the study was assessment of the changes in serum alanine aminotransferase (ALT) levels from baseline to week 12, while the secondary endpoints included the evaluation of liver inflammation, steatosis, and fibrosis parameters and markers. RESULTS: SNP-630 treatment in mice improved inflammation, liver steatosis, and fibrosis compared with that in the MASH control group. Both SNP-630 and SNP-630-MS treatments markedly reduced ALT levels, hepatic triglyceride content, and the expression of inflammatory cytokines monocyte chemoattractant protein 1 and fibrotic collagen (i.e., Col1a1, Col3a1, and Timp1) in mice. In the clinical trial, patients treated with SNP-630-MS exhibited significant improvement in ALT levels at week 12 compared with baseline levels, with no reports of severe adverse events. This improvement in ALT levels surpassed that achieved with most other MASH candidates. SNP-630-MS demonstrated potential antifibrotic effects, as evidenced by a significant decrease in the levels of fibrogenesis-related biomarkers such as CCL4, CCL5, and caspase 3. Subgroup analysis using FibroScan measurements further indicated the efficacy of SNP-630-MS in ameliorating liver fibrosis. CONCLUSIONS: SNP-630 and SNP-630-MS demonstrated favorable results in mice. SNP-630-MS showed excellent tolerability in mice and patients with MASH. Efficacy analyses indicated that SNP-630-MS improved liver steatosis and injury in patients with MASH, suggesting that SNP-630 and 630-MS are promising therapeutic options for MASH. Larger scale clinical trials remain warranted to assess the efficacy and safety of SNP-630 in MASH. TRIAL REGISTRATION: ClinicalTrials.gov NCT03868566. Registered 06 March 2019-Retrospectively registered, https://clinicaltrials.gov/study/NCT03868566.

Zaxinone Synthase overexpression modulates rice physiology and metabolism, enhancing nutrient uptake, growth and productivity.

The rice Zaxinone Synthase (ZAS) gene encodes a carotenoid cleavage dioxygenase (CCD) that forms the apocarotenoid growth regulator zaxinone in vitro. Here, we generated and characterized constitutive ZAS-overexpressing rice lines, to better understand ZAS role in determining zaxinone content and regulating growth and architecture. ZAS overexpression enhanced endogenous zaxinone level, promoted root growth and increased the number of productive tillers, leading to about 30% higher grain yield per plant. Hormone analysis revealed a decrease in strigolactone (SL) content, which we confirmed by rescuing the high-tillering phenotype through application of a SL analogue. Metabolomics analysis revealed that ZAS overexpressing plants accumulate higher amounts of monosaccharide sugars, in line with transcriptome analysis. Moreover, transgenic plants showed higher carbon (C) assimilation rate and elevated root phosphate, nitrate and sulphate level, enhancing the tolerance towards low phosphate (Pi). Our study confirms ZAS as an important determinant of rice growth and architecture and shows that ZAS regulates hormone homoeostasis and a combination of physiological processes to promote growth and grain yield, which makes this gene an excellent candidate for sustainable crop improvement.

Current landscape of mRNA technologies and delivery systems for new modality therapeutics.

Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.

Hybrids of two destructive subterranean termites established in the field, revealing a potential for gene flow between species.

Hybridization between invasive pest species may lead to significant genetic and economic impacts that require close monitoring. The two most invasive and destructive termite species worldwide, Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann), have the potential for hybridization in the field. A three-year field survey conducted during the dispersal flight season of Coptotermes in Taiwan identified alates with atypical morphology, which were confirmed as hybrids of the two Coptotermes species using microsatellite and mitochondrial analyses. Out of 27,601 alates collected over three years, 4.4% were confirmed as hybrid alates, and some advanced hybrids (>F1 generations) were identified. The hybrid alates had a dispersal flight season that overlapped with the two parental species 13 out of 15 times. Most of the hybrid alates were females, implying that mating opportunities beyond F1 may primarily be possible through female hybrids. However, the incipient colony growth results from all potential mating combinations suggest that only backcross colonies with hybrid males could sometimes lead to brood development. The observed asymmetrical viability and fertility of hybrid alates may critically reduce the probability of advanced-hybrid colonies being established in the field.

PoCXCL8, a teleost chemokine, exerts direct bactericidal, chemotactic/phagocytic, and NETs releasing properties, promoting host anti-bacterial immunity.

As an important CXC chemokine, CXCL8 plays pleiotropic roles in immunological response. In teleost, CXCL8 is involved in cell migration and bacterial invasion. However, the immune antibacterial function of CXCL8 in Japanese flounder (Paralichthys olivaceus) (PoCXCL8) is largely scarce. In this research, we investigated the antibacterial property and leukocyte activation of PoCXCL8. PoCXCL8 consists of 100 amino acid residues, with a conserved chemokine CXC domain. PoCXCL8 was expressed in various tissues, with the highest level in liver and the lowest level in muscle, and sharply induced by V. harveyi or E. tarda in liver, spleen, and head kidney. In vitro, the recombinant PoCXCL8 (rPoCXCL8) could bind to Bacillus subtilis, Edwardsiella tarda, Escherichia coli, Pseudomonas fluorescens, Vibrio anguillarum, Vibrio harveyi, Staphylococcus aureus, and Micrococcus luteus, affect the growth of E. coli, E. tarda, M. luteus, and P. fluorescens, and have a direct bactericidal effect on E. coli and E. tarda. Moreover, rPoCXCL8 was able to bind the outer membranal protein rPilA of E. tarda. In addition, rPoCXCL8 could bind to PBLs, activating the PBLs activity including chemotaxis, proliferation, phagocytosis, reactive oxygen species, acid phosphatase activity. At same time, rPoCXCL8 could induce neutrophil to generate neutrophil extracellular traps (NETs) and promote the expression of inflammatory genes including IL-1ß, IL6, MMP13, TNF-α, and NF-κB. In flounder, the presence of rPoCXCL8 could enhance the in vivo resistance to E. tarda in liver, spleen, and head kidney. Moreover, the PoCXCL8-deficient could attenuate the fish defense against E. tarda infection in in spleen and head kidney. In conclusion, these results provided new insights into the antibacterial properties of CXCL8 in P. olivaceus.

Solvent-polarity dependence of ultrafast excited-state dynamics of trans-4-nitrostilbene.

Ultrafast excited-state dynamics of the simplest nitrostilbenes, namely trans-4-nitrostilbene (t-NSB), was studied in solvents of various polarities with ultrafast broadband time-resolved fluorescence and transient absorption spectroscopies, and by quantum-chemical computations. The results revealed that the initially excited S1(ππ*) state deactivation dynamics is strongly influenced by the solvent polarity. Specifically, the t-NSB S1-state lifetime decreases by three orders of magnitude from ∼60 ps in high-polarity solvents to ∼60 fs in nonpolar solvents. The strong solvent-polarity dependence arises from the differences in dipole moments among the S1 and relevant states, including the major intersystem crossing (ISC) receiver triplet states, and therefore, the solvent polarity can modulate their relative energies and ISC rates. In nonpolar solvents, the sub-100 fs lifetime is due to a combination of efficient ISC and internal conversion. In medium-polarity solvents, the S1-state population decays via a competing ISC relaxation mechanism in a biphasic manner, and the ISC rates are found to obey the inverse energy gap law of the strong coupling case. In high-polarity solvents, the S1 state is stabilized to a much lower energy such that ISC becomes energetically infeasible, and the S1 state decays via barrier crossing along the torsion angle of the central ethylenic bond to the nonfluorescent perpendicular configuration. Regardless of the initial S1-state deactivation pathways in various solvents, the excited-state population is ultimately trapped in the metastable T1-state perpendicular configuration, at which a slower ISC occurs to bring the system to the ground state and bifurcate into either trans or cis form of NSB.

Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells.

Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.

High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer.

Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.

Brain natriuretic peptide as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis.

INTRODUCTION: Early identification of patients with sepsis at high risk of death remains a challenge, and whether brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a prognostic effect on patients with sepsis is controversial. Here, we clarified the prognostic value of BNP and NT-proBNP and sought to establish suitable cutoff values and intervals. METHODS: We searched five databases to identify studies that met the inclusion criteria. The primary outcomes were the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and corresponding 95% credible interval (95% CI) of BNP and NT-proBNP. The secondary outcomes were the sensitivity and specificity of BNP or NT-proBNP in subgroup analyses. RESULTS: Forty-seven studies were included in our meta-analysis. The pooled sensitivity of NT-proBNP (0.77 [0.68, 0.84]) was weaker than that of BNP (0.82 [0.76, 0.87]), the pooled specificity of NT-proBNP (0.70 [0.60, 0.77]) was less than that of BNP (0.77 [0.71, 0.82]), and the AUC of BNP (0.87 [0.83-0.89]) was greater than that of NT-proBNP (0.80 (0.76-0.83]). The results of the subgroup analysis showed that the cutoff range of 400-800 pg/mL for BNP had high sensitivity (0.86 [0.74-0.98]) and specificity (0.87 [0.81-0.93]) and was probably the most appropriate cutoff range. CONCLUSIONS: Elevated levels of BNP and NT-proBNP were significantly related to the mortality of patients with sepsis and had a moderate prognostic value in predicting the mortality of patients with sepsis. In addition, our meta-analysis preliminarily established appropriate cutoff values for BNP and NT-proBNP.

Direct Degradation of Fresh and Dried Macroalgae by Agarivorans albus B2Z047.

Marine macroalgae are increasingly recognized for their significant biological and economic potential. The key to unlocking this potential lies in the efficient degradation of all carbohydrates from the macroalgae biomass. However, a variety of polysaccharides (alginate, cellulose, fucoidan, and laminarin), are difficult to degrade simultaneously in a short time. In this study, the brown alga Saccharina japonica was found to be rapidly and thoroughly degraded by the marine bacterium Agarivorans albus B2Z047. This strain harbors a broad spectrum of carbohydrate-active enzymes capable of degrading various polysaccharides, making it uniquely equipped to efficiently break down both fresh and dried kelp, achieving a hydrolysis rate of up to 52%. A transcriptomic analysis elucidated the presence of pivotal enzyme genes implicated in the degradation pathways of alginate, cellulose, fucoidan, and laminarin. This discovery highlights the bacterium's capability for the efficient and comprehensive conversion of kelp biomass, indicating its significant potential in biotechnological applications for macroalgae resource utilization.

Assessing the Clinical Effectiveness of an Exergame-Based Exercise Training Program Using Ring Fit Adventure to Prevent and Postpone Frailty and Sarcopenia Among Older Adults in Rural Long-Term Care Facilities: Randomized Controlled Trial.

BACKGROUND: Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. OBJECTIVE: We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. METHODS: This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. RESULTS: We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). CONCLUSIONS: The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fmed.2022.1071409.

Three-Dimensional Human Posture Recognition by Extremity Angle Estimation with Minimal IMU Sensor.

Recently, posture recognition technology has advanced rapidly. Herein, we present a novel posture angle calculation system utilizing a single inertial measurement unit and a spatial geometric equation to accurately identify the three-dimensional (3D) motion angles and postures of both the upper and lower limbs of the human body. This wearable system facilitates continuous monitoring of body movements without the spatial limitations or occlusion issues associated with camera-based methods. This posture-recognition system has many benefits. Providing precise posture change information helps users assess the accuracy of their movements, prevent sports injuries, and enhance sports performance. This system employs a single inertial sensor, coupled with a filtering mechanism, to calculate the sensor's trajectory and coordinates in 3D space. Subsequently, the spatial geometry equation devised herein accurately computed the joint angles for changing body postures. To validate its effectiveness, the joint angles estimated from the proposed system were compared with those from dual inertial sensors and image recognition technology. The joint angle discrepancies for this system were within 10° and 5° when compared with dual inertial sensors and image recognition technology, respectively. Such reliability and accuracy of the proposed angle estimation system make it a valuable reference for assessing joint angles.

General anesthesia vs. conscious sedation and local anesthesia for endovascular treatment in patients with posterior circulation acute ischemic stroke: An updated systematic review and meta-analysis.

INTRODUCTION: The best anesthetic choice for patients with acute posterior circulation stroke during endovascular treatment (EVT) remains uncertain. METHOD: We searched five databases to identify studies that met the inclusion criteria. Our primary outcome measure was functional independence (FI). Secondary outcomes were 3-month mortality, any intracranial hemorrhage (ICH), symptomatic ICH (sICH), successful reperfusion, and procedure- and ventilator-associated complications. RESULTS: A total of 10 studies were included in our meta-analysis. No significant differences were detected between the general anesthesia (GA) and conscious sedation and local anesthesia (CS/LA) groups in 3-month FI (nine studies; OR=0.69; 95% CI 0.45-1.06; P=0.083; I2=66%;), 3-month mortality (nine studies; OR=1.41; 95% CI 0.94-2.11; P=0.096; I2=61.2%;), any ICH (three studies; OR=0.75; 95% CI 0.44-1.25; P=0.269; I2=0%;), or sICH (six studies; OR=0.64; 95% CI 0.40-1.04; P=0.073; I2=0%;). No significant differences were observed for successful reperfusion (10 studies; OR=1.17; 95% CI 0.91-1.49; P=0.219; I2=0%;), procedure-related complications (four studies; OR=1.14; 95% CI 0.70-1.87; P=0.603; I2=7.9%;), or respiratory complications (four studies; OR=1.19; 95% CI 0.61-2.32; P=0.616; I2=64.9%;) between the two groups. CONCLUSIONS: Our study showed no differences in 3-month FI, 3-month mortality, and successful reperfusion between patients treated with GA and those treated with CS/LA. Additionally, no increased risk of hemorrhagic transformation or pulmonary infection was observed in the CS/LA group. These results indicate that CS/LA may be an EVT option for acute posterior circulation stroke patients.

Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Optimal Post-Operative Nalbuphine Dose Regimen: A Randomized Controlled Trial in Patients with Laparoscopic Cholecystectomy.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

HCV Microelimination for High-risk Special Populations.

The World Health Organization has set tremendous goals to eliminate viral hepatitis by 2030. However, most countries are currently off the track for achieving these goals. Microelimination is a more effective and practical approach that breaks down national elimination targets into goals for smaller and more manageable key populations. These key populations share the characteristics of being highly prevalent for and vulnerable to hepatitis C virus (HCV) infection. Microelimination allows for identifying HCV-infected people and linking them to care more cost-effectively and efficiently. In this review, we discuss the current obstacles to and progress in HCV microelimination in special populations, including uremic patients undergoing hemodialysis, people who inject drugs, incarcerated people, people living in hyperendemic areas, men who have sex with men with or without human immunodeficiency virus (HIV) infection, transgender and gender-diverse populations, and sex workers. Scaling up testing and treatment uptake to achieve HCV microelimination may facilitate global HCV elimination by 2030.