Browse Articles

Emotion-BIND for multimodal emotion recognition and reasoning

Small subunit M20 augments inhibitory phosphorylation of MYPT1 in myosin light chain phosphatase by inhibiting autodephosphorylation

Smooth muscle myosin light chain phosphatase (MLCP), composed of a catalytic subunit PP1c and large and small noncatalytic subunits (MYPT1 and M20, respectively), is a key mediator of Rho-associated coiled-coil-containing kinase (RhoA-ROCK) signaling in cytoskeletal regulation. Phosphorylation of MYPT1 at Thr696 and Thr853 inhibits MLCP activity and augments MLC phosphorylation and smooth muscle contraction, whereas the functions of M20 remain undefined. To elucidate the functional significance of M20 in MLCP regulation, the present study compared the biochemical and structural properties of recombinant MLCP trimer (PP1c, MYPT1, and M20) and dimer (PP1c and MYPT1) complexes. While the rate of MYPT1 phosphorylation at Thr696 and Thr853 by ROCK2 in the presence of calyculin A was indistinguishable between the trimer and dimer complexes, the subsequent autodephosphorylation initiated by ROCK2 inhibition was significantly slower in the trimer. In the absence of calyculin A, phosphorylation in the trimer was greater than in the dimer. A dimer containing C-terminally truncated MYPT1 (Δ931 to 1030) mimicked trimer properties. Pull-down assays demonstrated the interactions of MYPT1–M20 and MYPT1–MYPT1, which were abolished by MYPT1 (Δ931 to 1030). High-speed atomic force microscopy revealed a superdimer complex consisting of two MLCP dimers tethered to the C-terminal region, whereas the trimer retained a single entity. These findings reveal a function of M20 that augments the inhibitory phosphorylation of MYPT1 by preventing superdimer formation mediated by the C-terminal region of MYPT1 and suppressing autodephosphorylation. Knockdown of M20 decreased the basal phosphorylation of MYPT1. M20 thus maintains MLCP in the inhibited state at basal conditions.

Dual-Stream deep learning for multimodal feature fusion and classification of balance control in elite freestyle aerial skiers

Balance control is a key determinant of stable landing in elite freestyle aerial skiing. Rapid and precise identification of subtle differences in athletes’ balance-stability regulation is a prerequisite for targeted, evidence-based training. Conventional balance assessment typically relies on force-platform measurements of the center of pressure (COP) trajectory and subsequent time-, frequency-, and time–frequency–domain analyses. However, these indices have limited ability to capture the complex dynamics of postural control and to discriminate fine-scale differences in balance regulation among highly trained freestyle skiing aerials athletes.To address this limitation, we developed a dual-stream deep learning model that fuses time–frequency image features with COP-based statistical descriptors to classify subtle variations in balance regulation. Twenty-five elite freestyle skiing aerials athletes were recruited and performed quiet standing under two conditions: (i) bipedal stance on a stable surface with eyes open and (ii) bipedal stance on an unstable surface with eyes open. COP trajectories were recorded and their multiscale entropy computed; K-means clustering was used to stratify participants into high-, medium-, and low-stability groups. The extracted time–frequency and statistical features were then fed into the dual-stream deep learning framework for model training and validation.The proposed model achieved approximately 95% classification accuracy in distinguishing data-driven COP-based stability strata, suggesting potential utility for the sensitive assessment of balance-regulation patterns in elite freestyle skiing aerials athletes.

Assessment of the precipitation deficit for rain-fed winter wheat in the Mediterranean coastal zone using the Agricultural Standardized Precipitation Index

Correction for Sen et al., mTOR signaling governs the formation of epithelial apical projections via S6K1–RhoA and aPKC–Lgl2 axes

Expression of Concern: Deep CNN-based detection of cardiac rhythm disorders using PPG signals from wearable devices

Robustness analysis of simulated biochip signal-based salmonella serovar classification under noise and sensor drift perturbations

Classification models for KCNQ1 variants distinguish functional and trafficking effects to enhance pathogenicity interpretation

Missense variants in the potassium channel KCNQ1 underlie most cases of congenital long QT syndrome (LQTS), one of the most common genetic arrhythmias. Variants affect protein stability, trafficking, and function, which are measurable properties that support variant interpretation. Leveraging the extensive experimental data generated by our laboratories, we developed random forest classifiers that predict seven KCNQ1 metrics: four electrophysiology and three trafficking measurements. The features for our classifiers integrate predictions from large machine learning models with protein-specific biophysical values, outperforming using either set of features alone. We applied our classifiers to interpret ClinVar variants of uncertain significance and AlphaMissense-ambiguous variants and developed global dysfunction and mistrafficking scores which distinguished benign from pathogenic variants. Global scores complemented AlphaMissense predictions, linking variants with LQTS-causing mechanisms. While effective for KCNQ1, our approach to variant prediction is generalizable to other ion channels and we recommend systematic benchmarking as done in this work to fully assess performance of future variant effect predictors.

Expression of Concern: The effects of learning experience on college students’ deep english learning: A study of the chain mediation effect of motivation and strategy

Genomic insights of lipid content in rice bran oil through M-QTL analysis

Fluid polarity shifts initiate and amplify preferential flow in clay-rich media

Preferential flow governs fluid and solute transport across scales from micropores to regional watersheds, yet it is commonly attributed to static pore-structure heterogeneity. Here, we show that fluid polarity can actively reorganize pore networks and amplify preferential flow in kaolinite-rich clay media. In permeation experiments, replacing water with a low-polar hydrofluoroether triggers early breakthrough (~0.4 d) and permeability up to ~62.7× higher than predicted by standard relative permeability functions at only 18.8% low-polar saturation. Multiscale imaging and porosimetry show a transition from unimodal microporosity to connected pore-fracture bimodal architectures. Interfacial measurements indicate that low-polar fluids weaken interparticle electrostatic repulsion and thereby reorganize pore space by reducing ineffective pores and activating latent connectivity. Guided by the cross-scale mechanistic chain, we establish a one-parameter relationship linking interfacial forces to ineffective porosity and integrate it into a coupled framework that reproduces preferential path development and permeability evolution across 21 clay-rich media and 24 fluids. These findings advance a cross-scale framework for polarity-driven transport dynamics and provide a basis for incorporating fluid polarity into predictive subsurface transport models in shallow clay-rich environments.

Patient perceptions and preferences during a community-based telehealth care model for moderate-to-severe hypertension in rural communities in Kenya and Uganda

Introduction Hypertension is a growing health concern in sub-Saharan Africa, yet access to care can be challenging, especially in rural areas. Overcoming barriers to hypertension care remains a priority. Pairing community health worker (CHW) and telehealth modalities offers one way to extend the reach of hypertension care without overburdening patients or healthcare systems in rural areas. Methods This qualitative study was nested within the SEARCH Sapphire pilot randomised controlled trial testing hypertension treatment through CHW-facilitated, clinician-driven telehealth (intervention) compared to clinic-based care (control) for adults aged ≥40 years with moderate-severe hypertension in rural western Kenya and southwestern Uganda. We conducted audio-recorded, in-depth, semi-structured interviews with purposively selected healthcare providers (clinicians and CHWs; N = 15) and participants (N = 40) between January-April 2023 to explore hypertension diagnosis and linkage to care; experiences with community hypertension care; family and work contexts; and the integration of telehealth into clinic and CHW workflows. Results Overall, participants felt satisfied with community-delivered telehealth care for hypertension. Participants noted community-based care saved on transport costs and reached those who were unwell or who lived far from clinic. Intervention arm participants felt CHWs were suitable for routine hypertension care, worked closely with clinicians, and could increase health literacy within the community. Participants desired a model with clear communication and involvement of the facility-based clinician, CHW, and participant. Providers found telehealth to be of similar quality to clinic-based care for routine hypertension treatment, though noted that clinic-based care is at times needed for more comprehensive clinical evaluation or to provide additional healthcare services. Conclusions Participants and providers indicated overall positive attitudes and receptivity to CHW-facilitated telehealth for hypertension care. CHW-delivered telehealth for community-based hypertension care offers one way to improve hypertension treatment outcomes in a manner that prioritizes patient-centeredness and maintains care quality. Trial Registration NCT04810650 Registered on 2021-03-18.

Temperature-induced shift in 21st-century Amazon droughts

Abstract The Amazon Basin (AB) has been experiencing a transition in hydroclimatic extremes induced by climate change; however, the relative contributions of precipitation deficits versus rising atmospheric evaporative demand (AED) remain poorly understood. Here, we analyzed and ranked AB droughts from 1980 to 2024, revealing that the 2023/24 event was unprecedented, affecting 88% of the basin with a magnitude four times greater than the average top-5 droughts. Notably, other years since 2020 also appear in the top rankings, underscoring how extreme conditions have persisted and intensified since the beginning of the decade. Our analysis of the AED contribution suggests a regime shift occurring during the 21st century. While earlier droughts were primarily precipitation-driven, the post-2005 era is characterized by a temperature-driven regime, where climate change-induced warming increases AED, acting as the primary intensifying mechanism for exceptional drought events. This intensification is further linked to sea surface temperature anomalies in the Tropical Indian, Tropical Pacific, and North Atlantic oceans.

Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition

Reproductive aging in mice leads to estropause, characterized by estrous cycle irregularity and eventual cessation, yet its underlying mechanism remains unclear. Here, we present a comprehensive single-cell atlas of mouse ovaries across precisely defined reproductive stages—from young (regular cycling) through the estropausal transition (regular vs. irregular cycling) to post-estropause (acyclic)—and of ovary-specific senescent cells defined by high senescence-associated β-galactosidase activity. We mapped transcriptomic dynamics of ovarian aging and characterized the molecular features of ovarian senescent cells. Our analyses revealed that during the estropausal transition, irregularly cycling ovaries exhibited accelerated aging and cellular senescence features compared with regularly cycling counterparts, including increased transcriptional noise, altered conserved aging pathways such as oxidative phosphorylation and proteostasis, hormone dysregulation in granulosa cells, and elevated expression of the senescence marker Cdkn1a and senescence-associated secretory phenotype factors. This atlas delineates the cellular and molecular hallmarks of mouse ovarian aging and ovary-specific senescent cells, providing a resource for understanding the mechanisms underlying the estropausal transition.

Retraction: Involvement of NF-κB in the reversal of CYP3A down-regulation induced by sea buckthorn in BCG-induced rats

Antimicrobial performance and congo red adsorption of plant extract derived copper oxide nanoparticles

Cryo-EM reveals that <i>Escherichia coli</i> tRNA-transglycosylase can bind and act upon two tRNAs

Bacterial tRNA-guanine transglycosylases (TGT) are essential enzymes involved in tRNA modification, contributing to the virulence of multiple pathogens. TGT from Escherichia coli was the first protein of this family to be isolated and purified, and as such has served as a model enzyme for the biochemical characterization of TGTs. E. coli TGT is also one of the most disease-relevant TGTs, sharing high sequence identity with TGTs from several human pathogenic bacteria, including Shigella spp. and Salmonella spp. Notably, TGTs from some Shigella strains are sequence-identical to the E. coli enzyme. In addition, as a highly promiscuous enzyme, E. coli TGT has found use as an RNA-modification tool in chemical biology, enabling site-specific covalent RNA modification in vitro and in vivo. For these reasons, there has been significant interest in solving the structure of E. coli TGT. However, crystallization of E. coli TGT has proven difficult, and to date, structural insights have relied on surrogate TGT enzymes from other organisms. Here, we present the cryo-EM structure of E. coli TGT and its covalent intermediate with a full-length tRNA. Unexpectedly, the structure reveals that the E. coli TGT dimer binds and acts upon two tRNAs, which is unlike all other known TGTs. Closer analysis of the TGT–tRNA complex reveals several important interactions outside of the enzyme’s active site, that facilitate RNA binding and stabilize the conformational change of the tRNA anticodon loop. Based on these structural insights, we were able to design improved, high-affinity, TGT substrate RNA hairpins.

Experimental study of seepage-scour failure in geotextile tubes gap with damaged vertical sidewall

Geotextile tubes, hydraulically filled with a slurry of fine silt and water, have been variously applied in hydraulic and coastal engineering fields. However, geotextile damage poses a great threat to structures made of geotextile tubes. When a water head difference exists across the tube, the soil in damaged tubes is affected by the dual actions of seepage and scour. To investigate soil failure patterns and tendencies of damaged tubes under hydraulic action, a structural apparatus and the corresponding test method were designed. Four factors considered were the radius of the damaged area ( r 0 : 0.25–2.0 cm), the grain size distribution (Sand B C u  = 3.4, Sand E C u  = 50), the scouring flow velocity ( v : 0–4 cm/s), and the hydraulic gradient. The results showed that the scouring flow exerted a limited effect on the failure mode of sand in the tubes, and that the failure process of sand in the tubes could be divided into three stages including a stable, an initial erosion, and a cyclic sand outflow stage. The hydraulic gradient at the initial erosion stage was defined as the critical gradient( j cr ), which was interactively influenced by sand gradation, damage radius, and scouring flow velocity. Under identical conditions, Sand E exhibited a higher resistance against seepage-induced failure than Sand B. In terms of stability under varying conditions, for Sand B, increasing the damage radius (tested at flow velocities of 0–4 cm/s) reduced j cr by 94%–100%, while increasing the flow velocity (tested at damage radii of 0.25–2.0 cm) reduced j cr by 60%–100%. For Sand E, the corresponding reductions were 83%–95% and 58%–88%, respectively, further confirming Sand E’s superior erosion resistance.

Dual-target reduction in locally advanced nasopharyngeal carcinoma: omission of Ib/VIIb irradiation and medial boundary contraction of the CTV

The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway

Liver fibrosis is a progressive and life-threatening condition with no effective targeted treatments. Growing evidence indicates a two-way relationship between circadian rhythm and fibrogenesis, although the specific molecular signaling pathways involved are still not well understood. The molecular clock, which governs circadian rhythms, regulates metabolic and cellular functions, and its pharmacological manipulation has shown potential as a therapy for organ fibrosis. Although the liver’s molecular clock appeared resilient to the progression of chronic liver disease in humans from steatosis to fibrosis, detectable changes in the daily amplitude of clock genes were observed in a cohort of people living with obesity. We found a clock-controlled signaling pathway that drives hepatic stellate cell (HSC) activation, a key initiating event in fibrosis progression. Interfering with this pathway, either by disrupting the core regulator CLOCK:BMAL1 or activating the nuclear receptors REV-ERBs, significantly reduced HSC activation. We also identified transgelin as the downstream effector of clock-regulated HSC contractility, a characteristic of HSC activation. Transgelin is regulated indirectly by a BMAL1-CK1ε signaling pathway and directly by REV-ERBα. Our findings identify a hitherto undescribed mechanism that links the molecular clock to HSC activation and cell contractile function, which is relevant to human fibrotic diseases. This pathway provides several entry points for drugs to target and disrupt primary fibrogenic signaling. By connecting clock biology to the cellular processes that cause fibrosis, our work also offers a mechanistic basis for chronotherapeutic strategies against chronic liver disease.