Opposite Direction Research Articles

Impact of Socio-Demographic Attributes and Mutual Gaze of Virtual Humans on Users' Visual Attention and Collision Avoidance in VR.

This study investigated the extent that the non-verbal behaviors of virtual humans (VHs) and their socio-demographic attributes altered users' collision avoidance behaviors in Virtual Reality (VR). Users interacted with VHs representing different levels of ethnicities and gender, exhibiting different conditions of physical movement, and gaze behaviors. The VHs were depicted in three major ethnic conditions namely Asian, Caucasian, and Black. The physical movement states of the VHs were either static in the path of the user or walking toward the user in the opposite direction. The non-verbal gaze behavior of the VHs was either direct gaze or averted gaze. We used an HTC Vive tracking system to track users' performing real walking while we collected objective measures (i,e., continuous gaze, fixation gaze, clearance distance, and travel length), and subjective variables (i.e., game experiences and social presence). The results showed that the ethnicity of the VHs significantly impacted the gaze behavior of the users, and the gender of the VHs affected the user avoidance movement and their reciprocal gaze behavior. Our results revealed that users' physical movement, gaze behaviors, and collision avoidance were moderated by the VHs' perceived ethnicity, gender, and gaze behaviors. Understanding the impact of the socio-demographics attributes of VHs and their gaze behavior on users' collision avoidance is critical for applications in which users are navigating through virtual traffic, crowd, and other inter-personal simulations.

Confinement controls the directional cell responses to fluid forces

Our understanding of how fluid forces influence cell migration in confining environments remains limited. By integrating microfluidics with live-cell imaging, we demonstrate that cells in tightly-but not moderately-confined spaces reverse direction and move upstream upon exposure to fluid forces. This fluid force-induced directional change occurs less frequently when cells display diminished mechanosensitivity, experience elevated hydraulic resistance, or sense a chemical gradient. Cell reversal requires actin polymerization to the new cell front, as shown mathematically and experimentally. Actin polymerization is necessary for the fluid force-induced activation of NHE1, which cooperates with calcium to induce upstream migration. Calcium levels increase downstream, mirroring the subcellular distribution of myosin IIA, whose activation enhances upstream migration. Reduced lamin A/C levels promote downstream migration of metastatic tumor cells by preventing cell polarity establishment and intracellular calcium rise. This mechanism could allow cancer cells to evade high-pressure environments, such as the primary tumor.

Social sharing of emotion during the collective crisis of COVID-19.

We collected data from two sources - social media and online questionnaires - to investigate the emotional consequences of social sharing during the COVID-19 pandemic. Study 1 tracked and analysed sentiment of tweets posted over the course of a month in the crisis period and found that users who tweeted more frequently about COVID-19 expressed decreasing negative sentiment and increasing positive sentiment over time. Granger causality tests confirmed that this association was better interpreted in the forward direction (sharing levels predicting sentiment) than in the reverse direction (sentiment predicting sharing levels). Study 2 focused on immediate emotional consequences of sharing COVID-19-related events and found that participants reported improved overall affect about an event after sharing it, especially when that event was a personal experience rather than a news story. Reported positive feelings about both kinds of events were also significantly higher after sharing. Taken together, both studies suggested that social sharing is linked with emotional relief and may therefore help people to deal with their negative experiences during a persistent collective crisis.

Bidirectional Molecular Motors by Controlling Threading and Dethreading Pathways of a Linked Rotaxane.

Artificial molecular motors have been presented as models for biological molecular motors. In contrast to the conventional artificial molecular motors that rely on covalent bond rotation, molecular motors with mechanically interlocked molecules (MIM) have attracted considerable attention owing to their ability to generate significant rotational motion by dynamically shuttling macrocyclic components. The topology of MIM-type rotational molecular motors is currently limited to catenane structures, which require intricate synthetic procedures that typically produce a low synthetic yield. In this study, we develop a novel class of MIM-type molecular motors with a rotaxane-type topology. The switching of the threading/dethreading pathways of the linked rotaxane by protecting/deprotecting the bulky stopper group and changing the solvent polarity enables a net unidirectional rotation of the molecular motor. The threading/dethreading reaction rates were quantitatively evaluated through detailed spectroscopic investigations. Repeated net unidirectional rotation and switching of the direction of rotation were also achieved. Our findings demonstrate that linked rotaxanes can serve as MIM-type molecular motors with reversible rotational direction controlled by threading/dethreading reactions. These motors hold potential as components of molecular machinery.

Phase classification and transient effects of the start-up process of multi-functional pump station in pump mode

In the context of achieving the goal of carbon neutrality, multi-functional pump stations (MFPS) have been greatly developed as a new energy system in recent years. The MFPS can operate in forward direction in pump mode to pump water and in turbine mode in reverse direction to generate electricity. At present, the instability of the MFPS during start-up process (SUP) in pump mode has become the key to restricting the operating life and further development of MFPS. In this paper, based on the motion characteristics of the pump and the cut-off facility (COF), the SUP of the MFPS in pump mode is clearly classified. In order to reveal the transient effect during the SUP, the steady-state full characteristic experiment (SFCE) of the pump was carried out. The occurrence phase of the transient effect during the SUP is analyzed, and the deviation between the steady-state external characteristics and the transient characteristics is revealed. In this study, the evaluation formula of the start-up completion degree (SUCD) of the MFPS in pump mode is proposed for the first time, and the evaluation and identification of the start-up progress at different phases are completed. The results show that the water flow in the system is in a reverse flow state in the Phase I. The SUCD of Phase I is 17 %. In the Phase II, The high-speed jet flow in the pump flows to the inlet of the guide vane (GV), which gradually changes the mainstream direction in the GV. A certain vortex structure can be observed at the exit of the flap gate (FG). The SUCD of Phase II is 61 %. In the Phase I and II, the dimensionless head of transient simulation is much larger than that of SFCE. In the Phase III, the flow state in the impeller will gradually stabilize. The transient effect disappears and the pressure fluctuation intensity decreases. The SUCD of Phase III is 93 %. In the Phase IV, the separation vortex that persists from Phase I-III at the tail of the GV blades disappears. The diversion capacity at the gate increases, and significant annular flow can be observed near the FG.

Tagged particle behavior in a harmonic chain of direction-reversing active Brownian particles

Abstract We study the tagged particle dynamics in a harmonic chain of direction-reversing active Brownian particles, with the spring constant k, rotation diffusion coefficient D R , and directional reversal rate γ. We exactly compute the tagged particle position variance for quenched and annealed initial orientations of the particles. For well-separated time-scales, k − 1 , D R − 1 and γ −1, the strength of the spring constant k relative to D R and γ gives rise to different coupling limits, and for each coupling limit there are short, intermediate, and long-time regimes. In the thermodynamic limit, we show that, to the leading order, the tagged particle variance exhibits an algebraic growth t ν , where the value of the exponent ν depends on the specific regime. For a quenched initial orientation, the exponent ν crosses over from 3 to 1 / 2 , via intermediate values 5 / 2 or 1, depending on the specific coupling limits. However, for the annealed initial orientation, ν crosses over from 2 to 1 / 2 via an intermediate value 3 / 2 or 1 for the strong coupling limit and the weak coupling limit, respectively. An additional time-scale t N = N 2 / k emerges for a system with a finite number of oscillators N. We show that the behavior of the tagged particle variance across tN can be expressed in terms of a crossover scaling function, which we find exactly. Moreover, we study the velocity autocorrelation. Finally, we characterize the stationary state behavior of the separation between two consecutive particles by calculating the corresponding spatio-temporal correlation function.

Simulating droplet distribution characteristics in sprinkler irrigation using a modified ballistic model under multifactor coupling

External factors affecting the processes of sprinkler irrigation water flow generation, flight, and landing have not been thoroughly considered in existing ballistic models. This result indicates that ballistic models with better prediction effects under specific conditions are not sufficient for extension to multi-factor coupled scenarios in large-scale farmlands. Therefore, wind, evaporation, surface slope, and tilted sprinkler riser factors were comprehensively considered in this study. Differential equations for jet and droplet motion under the influence of wind, differential equations of droplet evaporation, sprinkler riser deflection angle matrix, and surface slope angle matrix were constructed to establish a droplet distribution model for sprinkler irrigation considering multifactor coupling using MATLAB 2018a software. The results showed that, under different working conditions, the data points of the droplet landing diameter, velocity, and angle were distributed near the 1:1 line. The Nash efficiency coefficients (NSE) for the droplet landing diameter, velocity, and angle varied from 0.821 to 0.932, 0.616 to 0.931, and 0.770 to 0.911, respectively. The increase in slope resulted in droplets with diameters larger than 4.63 mm concentrating on the land in the reverse slope direction. When the ambient temperature increases from 10 to 45 °C and the total evaporation rate increases from 0.45 to 4.37 %, the larger droplets have a larger area of contact with the air, and the higher the temperature, the greater the energy loss to the larger droplet diameters. The higher the wind speed, the more droplets in the downwind direction fall to the ground at a smaller landing angle, which can easily increase the risk of soil shear damage. If the sprinkler riser was tilted east, the droplets on both the east and west sides tended to be distributed centrally; the maximum droplet landing velocity occurred on the east side (tilted side), and the maximum droplet landing angle occurred on the west side. This study considers various factors that may affect the motion of sprinkler irrigation water flow, extends the application scenarios of the theoretical model, and improves the applicability of the theoretical model for sprinkler irrigation droplet motion in more complex and practical agricultural environments.

Observation of Topological Transition in Floquet Non-Hermitian Skin Effects in Silicon Photonics.

Non-Hermitian physics has greatly enriched our understanding of nonequilibrium phenomena and uncovered novel effects such as the non-Hermitian skin effect (NHSE) that has profoundly revolutionized the field. NHSE has been predicted in systems with nonreciprocal couplings which, however, are challenging to realize in experiments. Without nonreciprocal couplings, the NHSE can also emerge in systems with coexisting gauge fields and loss or gain (e.g., in Floquet non-Hermitian systems). However, such Floquet NHSE remains largely unexplored in experiments. Here, we realize the Floquet NHSEs in periodically modulated optical waveguides integrated on a silicon photonic platform. By engineering the artificial gauge fields induced by the periodical modulation, we observe various Floquet NHSE phases and unveil their rich topological transitions. Remarkably, we discover the transitions between the unipolar NHSE phases and an unconventional bipolar NHSE phase, which is accompanied by the directional reversal of the NHSEs. The underlying physics is revealed by the band winding in complex quasienergy space which undergoes a topology change from isolated loops with the same winding to linked loops with opposite windings. Our work unfolds a new route toward Floquet NHSEs originating from the interplay between gauge fields and dissipation effects, and thus offers fundamentally new ways for steering light and other waves.

Multi-objective optimization and artificial neural network models for enhancing the overall performance of a microchannel heat sink with fins inspired Tesla valve profile

Microchannel heat sinks (MCHSs) are advanced cooling systems used in various applications such as electronics cooling, thermal management of high-power microprocessors, and microelectronic devices. These heat sinks are designed to efficiently dissipate heat generated by electronic components to maintain optimal operating temperatures and ensure device reliability. Employing appropriate fins within MCHSs is a crucial strategy to enhance heat removal efficiency. Since few investigations have been performed on the simultaneous thermo-hydraulic features in microchannels with Tesla valves, this research addresses this gap by suggesting that the microchannels of a heat sink be reinforced with novel Tesla valve-shaped fins. Tesla valves are designed to offer different levels of resistance depending on the flow direction. This characteristic allows for selective control of pressure drop and heat transfer efficiency by simply switching the flow direction. Utilizing Tesla valve-shaped fins is an almost new approach that differentiates the current research from conventional designs. The advantage of this structure is that under different circumstances, depending on whether more heat transfer is required or less pressure drop (ΔP), the flow direction can be changed, and the maximum efficiency of the MCHS can be accessed. The other innovative aspect of this study lies in the integration of artificial neural network (ANN) models to optimize the efficiency of MCHSs equipped with Tesla valve-shaped fins. The simulations were conducted to characterize the flow and thermal features of the MCHS. Then, these data were used as the benchmark for training the ANN models. Four ANN models were introduced to anticipate the Nusselt number (Nu) and ΔP in each forward and reverse direction. The divider's acute angle (α), the divider's obtuse angle (β), and the divider's radius (R) were selected as the input data. Multi-objective optimization and genetic algorithms were used to achieve the optimal conditions. In the optimal thermal design (Setting 2: MCHS with fin variables of α = 60 β = 180, and R = 80 μm in reverse flow direction), the overall performance had a significant enhancement of 57.1 % compared to the device lacking fins. Furthermore, in Setting 2, the overall performance of the MCHS and its diodicity experienced notable improvements of approximately 12.1 % and 38.5 %, respectively. Implementing the parameters of Setting 5 (MCHS with fin variables of α = 60, β = 152.32, and R = 73.10 μm in forward direction) during fin production resulted in a notable enhancement of about 41.1 % in the device's overall performance.

Directionality Reversal and Shift of Rotational Axis in a Hemithioindigo Macrocyclic Molecular Motor.

Molecular motors are central driving units for nanomachinery, and control of their directional motions is of fundamental importance for their functions. Light-driven variants use easy to provide, easy to dose, and waste-free fuel with high energy content, making them particularly interesting for applications. Typically, light-driven molecular motors work via rotations around dedicated chemical bonds where the directionality of the rotation is dictated by the steric effects of asymmetry in close vicinity to the rotation axis. In this work, we show how unidirectional rotation around a virtual axis can be realized by reprogramming a molecular motor. To this end, a classical light-driven motor is restricted by macrocyclization, and its intrinsic directional rotation is transformed into a directional rotation of the macrocyclic chain in the opposite direction. Further, solvent polarity changes allow to toggle the function of this molecular machine between a directional motor and a nondirectional photoswitch. In this way, a new concept for the design of molecular motors is delivered together with elaborate control over their motions and functions by simple solvent changes. The possibility of sensing the environmental polarity and correspondingly adjusting the directionality of motions opens up a next level of control and responsiveness to light-driven nanoscopic motors.

OsLdh7, a rice lactate dehydrogenase, confers stress resilience in rice under cadmium stress through NAD+/NADH regulation

Lactate dehydrogenase (Ldh, EC 1.1.1.27), an oxidoreductase enzyme catalyses the interconversion of pyruvate to L-lactate and vice-versa with concomitant oxidation and reduction of NADH and NAD+. The enzyme functions as a ROS sensor and mitigates stress response by maintaining NAD+/NADH homeostasis. In this study, we delineated the role of the Ldh enzyme in imparting cadmium stress tolerance in rice. Previously, we identified a putatively active Ldh in rice (OsLdh7) through in-silico modelling. Biochemical characterization of the OsLdh7 enzyme revealed it to be optimally active at pH 6.6 in the forward direction and pH 9 in the reverse direction. Overexpression of OsLdh7 in rice cv.IR64, increased tolerance of the transgenic lines to cadmium stress compared to the wild type (WT) at both seedling and reproductive stages. The transgenic lines showed increased enzyme activity in the reverse direction under cadmium stress, attributed to elevated cytosolic pH resulting from increased calcium concentration. This increased NADH content is highly essential for functioning of the ROS scavenging enzymes, RbohD and MPK6. qPCR analysis revealed that the overexpression lines had increased transcript abundance of these genes indicating an effective ROS scavenging mechanism. Additionally, the overexpression lines showed an efficient cadmium sequestration mechanism compared to the WT by increasing the transcript levels of the vacuolar transporters of cadmium as well as total phytochelatin content. Thus, our findings indicated OsLdh7 imparts cadmium stress tolerance in rice through a two-pronged approach by mitigating ROS and sequestering cadmium ions, highlighting its potential for crop improvement programs.

On reversal of wave-generated longshore currents at tidal frequencies on dissipative beaches contiguous to a mesotidal estuary, S.E coast of Nigeria

Reversals in wave-generated longshore currents in surf zones occur at different temporal and spatial scales. Along coastlines with tidal channel openings with well-developed mouth bars or ebb-tidal deltas, the reversal mechanism is often attributed to the mouth bar – induced refraction of the shoaling waves. This reversal mechanism is characterized by convergence of longshore currents from the adjoining surf zones at the mouth of the tidal channel. Simultaneous half-hourly monitoring of wave-generated longshore currents over 50 successive (daylight) semi-diurnal tidal cycles in beach surf zones adjoining the Qua Iboe River estuary, S.E coast of Nigeria showed the above reversal pattern during flooding stage only. The converse pattern, where the surf zone longshore currents diverged away from the mouth of the estuary, was observed during ebbing stage. Both surf zones showed flow direction inversion with respect to each other, with velocity vector correlation coefficient r > − 0.8 in over 80 % of the data set. Instances of comparable flow direction (<10 %) were also recorded. Tidal processes are implicated in the documented results. Direction-averaged longshore current velocities, typically in the 15–60 cm/s range, attained highest values in both surf zones at about spring tide phase. Also, tidal cycle-residual longshore current maximum and minimum velocities occurred close to spring and neap tide, respectively. Only 30 % of the residual velocities were eastward directed in the up-drift surf zone as against 80 % in the down-drift counterpart. Given the prevailing southwesterly waves, the present results negate the assertion that reversal in longshore current direction in this offset shoreline setting is exclusively a consequence of wave refraction by mouth bar morphology. The reversing pattern of the longshore currents over a tidal cycle is well explained by incorporating interacting effects of shoaling waves with tide-induced oscillations in water level as well as the estuarine flow.

Dynamic evolution of amplitude and position of geomagnetic secular acceleration pulses since 2000

Recent studies on the behavior of geomagnetic secular acceleration (SA) pulses have provided a basis for understanding the dynamic processes in the Earth’s core. This analysis statistically evaluates the evolution of the SA pulse amplitude and position since 2000 by computing the three-year difference in SA with the CHAOS-7 geomagnetic field model (CHAOS-7.17 release). Furthermore, the study explores the correlation between the acceleration pulse amplitude and geomagnetic jerks and the dynamic processes of alternating variation and polarity reversal of pulse patches over time. Research findings indicate that the variation in pulse amplitude at the Core Mantle Boundary (CMB) closely resembles that observed at the Earth’s surface, with an average period of 3.2 years. The timing of peak pulse amplitude aligns with that of the geomagnetic jerk, suggesting its potential utility as a novel indicator for detecting geomagnetic jerk events. The acceleration pulses are the strongest near the equator (2°N) and more robust in the high-latitude region (68°S) of the Southern Hemisphere, indicating that the variation is more dramatic in the Southern Hemisphere. The acceleration pulses fluctuate unevenly in the west-east direction, with characteristics of local variation. In the Western Hemisphere, the pulse patches are distributed near the equator, exhibiting an evident westward drifting mode. The positive and negative patches alternate in time, displaying a polarity reversal in the west-east direction, with an average interval of approximately 32°. These characteristics can be attributed to the rapid magnetic field fluctuations disclosed by the model of stratification at the top of the Earth’s core. In the Eastern Hemisphere, the pulses are weaker between 10°E and 60°E, with the most active pulses occurring around 80°E to 105°E and near 150°E. The pulse patches exhibit a broader distribution in the north-south direction, with relatively strong patches still occurring near 40°N and 40°S. These local variation characteristics match the actual cases of zonal flows and geostrophic Alfvén waves in the Earth’s core.

Reverse cannulation method as a strategy for aortic aneurysm surgery: A computational fluid dynamics study on minimizing neurological risks

ObjectivesTo evaluate the blood flow velocity and wall shear stress in total arch replacement with a “shaggy” aorta, using computational fluid dynamics, and determine the optimal cannulation method. MethodsA patient-specific aortic arch aneurysm model was constructed by using computed tomography scans. Three cannulas were assessed, as follows: dispersive with a steep angle, dispersive with a gentle angle, and the endo-hole type. The cannula tips were oriented toward the aortic arch (standard direction) and aortic root (reversed direction), with an ideal angle (base orientation: 0°), tip orientations rotated 20° clockwise and counterclockwise from the base orientation. The variables of interest included the blood flow velocity, streamlines, wall shear stress, and flow distribution. ResultsThe standard direction resulted in variable accelerated flow and wall shear stress locations based on cannula tip orientation, leading to unstable cerebral branch flow. Minor deviation in the cannula tip angle and cannula type led to significant alterations in flow distribution. Conversely, in the reverse direction for all cannulas, no accelerated blood flow was observed in the proximal aortic arch or cerebral vessel ostia even with angular adjustments, helping maintain a stable cerebral branch flow. Minimal variation in blood flow distribution was observed across all cannula types and angles. ConclusionOur simulations indicate that, irrespective of the cannula type or orientation, directing the cannula tip toward the aortic root (reversed direction) prevents accelerated blood flow in critical areas, suggesting its potential as an optimal approach for aortic arch surgery in “shaggy” aorta cases.

Passive and active field theories for disease spreading

The worldwide COVID-19 pandemic has led to a significant growth of interest in the development of mathematical models that allow to describe effects such as social distancing measures, the development of vaccines, and mutations. Several of these models are based on concepts from soft matter theory. Considerably less well investigated is the reverse direction, i.e. how results from epidemiological research can be of interest for the physics of colloids and polymers. In this work, we consider the susceptible-infected-recovered (SIR)-dynamical density functional theory (DDFT) model, a combination of the SIR model from epidemiology with DDFT from nonequilibrium soft matter physics, which allows for an explicit modeling of social distancing. We extend the SIR-DDFT model both from an epidemiological perspective by incorporating vaccines, asymptomaticity, reinfections, and mutations, and from a soft matter perspective by incorporating noise and self-propulsion and by deriving a phase field crystal (PFC) model that allows for a simplified description. On this basis, we investigate via computer simulations how epidemiological models are affected by the presence of non-reciprocal interactions. This is done in a numerical study of a zombie outbreak.

Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family

2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary α–carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation.

Bidirectional causal associations between aging and major mental disorders: A population-based study using the two-sample mendelian randomization method from the UK biobank (AM-SRNMA 002)

AimsWhile observational studies have suggested associations linking aging and mental disorders, the question of causality has remained unclear. This study aimed to explore the causal relationship between aging level and major mental disorders. MethodsWe utilized Two-Sample Mendelian randomization (2SMR) with mental disorders data and aging indicators information from an extensive genome-wide association study (GWAS) database. The GWAS database is a comprehensive resource that compiles genetic association data, encompassing a sample size of over 450,000 individuals. We employed five methods for 2SMR and single nucleotide polymorphisms were chosen as instrumental variables. ResultsOur analyses consistently supported a bidirectional causal association between the Frailty Index (FI) and Major Depressive Disorder (MDD). Furthermore, our findings indicated potential influences, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BD) affecting GrimAge, and Anxiety Disorder (AD) impacting Left Hand Grip Strength (LHGS). In contrast, we observed no significant correlations for other mental disorders on FI, Telomere Length (TL), GrimAge, Appendicular Lean Mass (ALM), and LHGS. In the reverse direction, FI showed a significant impact on the risk of MDD, AD, and ADHD, while LHGS affected the risk of MDD. Importantly, no significant associations were found between other factors and the risk of MDD, BD, AD, Schizophrenia (SZ), and ADHD. ConclusionsThis 2SMR analysis has presented evidence for a bidirectional causal relationship between FI and MDD, while the relationship between ADHD, BD, and GrimAge should be more considered. Our study provides genetic evidence supporting a causal link between aging indicators and several mental illnesses.

Thg1 family 3'-5' RNA polymerases as tools for targeted RNA synthesis.

Members of the 3'-5' RNA polymerase family, comprised of tRNAHis guanylyltransferase (Thg1) and Thg1-like proteins (TLPs), catalyze templated synthesis of RNA in the reverse direction to all other known 5'-3' RNA and DNA polymerases. Discovery of enzymes capable of this reaction raised the possibility of exploiting 3'-5' polymerases for post-transcriptional incorporation of nucleotides to the 5'-end of nucleic acids without ligation, and instead by templated polymerase addition. To date, studies of these enzymes have focused on nucleotide addition to highly structured RNAs, such as tRNA and other non-coding RNA. Consequently, general principles of RNA substrate recognition and nucleotide preferences that might enable broader application of 3'-5' polymerases have not been elucidated. Here, we investigated the feasibility of using Thg1 or TLPs for multiple nucleotide incorporation to the 5'-end of a short duplex RNA substrate, using a templating RNA oligonucleotide provided in trans to guide 5'-end addition of specific sequences. Using optimized assay conditions, we demonstrated a remarkable capacity of certain TLPs to accommodate short RNA substrate-template duplexes of varying lengths with significantly high affinity, resulting in the ability to incorporate a desired nucleotide sequence of up to 8 bases to 5'-ends of the model RNA substrates in a template-dependent manner. This work has further advanced our goals to develop this atypical enzyme family as a versatile nucleic acid 5'-end labeling tool.

Impact of acupuncture on ischemia/reperfusion injury: Unraveling the role of miR-34c-5p and autophagy activation

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI.

Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study.

The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs. Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren's syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality. Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including "CD25++ CD8+ T cell % CD8+ T cell" (mediation proportion: 6.2%) and "CD3 on activated CD4 regulatory T cell" (5.4%). Additionally, "CD127 on granulocyte" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05). This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.