Self-enhanced mobility enables vortex pattern formation in living matter.

Ranging from subcellular organelle biogenesis to embryo development, the formation of self-organized structures is a hallmark of living systems. Whereas the emergence of ordered spatial patterns in biology is often driven by intricate chemical signalling that coordinates cellular behaviour and differentiation1-4, purely physical interactions can drive the formation of regular biological patterns such as crystalline vortex arrays in suspensions of spermatozoa5 and bacteria6. Here we discovered a new route to self-organized pattern formation driven by physical interactions, which creates large-scale regular spatial structures with multiscale ordering. Specifically we found that dense bacterial living matter spontaneously developed a lattice of mesoscale, fast-spinning vortices; these vortices each consisted of around 104-105 motile bacterial cells and were arranged in space at greater than centimetre scale and with apparent hexagonal order, whereas individual cells in the vortices moved in coordinated directions with strong polar and vortical order. Single-cell tracking and numerical simulations suggest that the phenomenon is enabled by self-enhanced mobility in the system-that is, the speed of individual cells increasing with cell-generated collective stresses at a given cell density. Stress-induced mobility enhancement and fluidization is prevalent in dense living matter at various scales of length7-9. Our findings demonstrate that self-enhanced mobility offers a simple physical mechanism for pattern formation in living systems and, more generally, in other active matter systems10 near the boundary of fluid- and solid-like behaviours11-17.

Viscoelastic control of spatiotemporal order in bacterial active matter.

Active matter consists of units that generate mechanical work by consuming energy1. Examples include living systems (such as assemblies of bacteria2-5 and biological tissues6,7), biopolymers driven by molecular motors8-11 and suspensions of synthetic self-propelled particles12-14. A central goal is to understand and control the self-organization of active assemblies in space and time. Most active systems exhibit either spatial order mediated by interactions that coordinate the spatial structure and the motion of active agents12,14,15 or the temporal synchronization of individual oscillatory dynamics2. The simultaneous control of spatial and temporal organization is more challenging and generally requires complex interactions, such as reaction-diffusion hierarchies16 or genetically engineered cellular circuits2. Here we report a simple technique to simultaneously control the spatial and temporal self-organization of bacterial active matter. We confine dense active suspensions of Escherichia coli cells and manipulate a single macroscopic parameter-namely, the viscoelasticity of the suspending fluid- through the addition of purified genomic DNA. This reveals self-driven spatial and temporal organization in the form of a millimetre-scale rotating vortex with periodically oscillating global chirality of tunable frequency, reminiscent of a torsional pendulum. By combining experiments with an active-matter model, we explain this behaviour in terms of the interplay between active forcing and viscoelastic stress relaxation. Our findings provide insight into the influence of bacterial motile behaviour in complex fluids, which may be of interest in health- and ecology-related research, and demonstrate experimentally that rheological properties can be harnessed to control active-matter flows17,18. We envisage that our millimetre-scale, tunable, self-oscillating bacterial vortex may be coupled to actuation systems to act a 'clock generator' capable of providing timing signals for rhythmic locomotion of soft robots and for programmed microfluidic pumping19, for example, by triggering the action of a shift register in soft-robotic logic devices20.

Geometrical control of interface patterning underlies active matter invasion.

Interaction between active materials and the boundaries of geometrical confinement is key to many emergent phenomena in active systems. For living active matter consisting of animal cells or motile bacteria, the confinement boundary is often a deformable interface, and it has been unclear how activity-induced interface dynamics might lead to morphogenesis and pattern formation. Here, we studied the evolution of bacterial active matter confined by a deformable boundary. We found that an ordered morphological pattern emerged at the interface characterized by periodically spaced interfacial protrusions; behind the interfacial protrusions, bacterial swimmers self-organized into multicellular clusters displaying +1/2 nematic defects. Subsequently, a hierarchical sequence of transitions from interfacial protrusions to creeping branches allowed the bacterial active drop to rapidly invade surrounding space with a striking self-similar branch pattern. We found that this interface patterning is geometrically controlled by the local curvature of the interface, a phenomenon we denote as collective curvature sensing. Using a continuum active model, we revealed that the collective curvature sensing arises from enhanced active stresses near high-curvature regions, with the active length scale setting the characteristic distance between the interfacial protrusions. Our findings reveal a protrusion-to-branch transition as a unique mode of active matter invasion and suggest a strategy to engineer pattern formation of active materials.

Reduced surface accumulation of swimming bacteria in viscoelastic polymer fluids.

Surface-associated bacterial communities flourish in nature and in the body of animal hosts with abundant macromolecular polymers. It is unclear how the endowed viscoelasticity of polymeric fluids influences bacterial motile behavior in such environments. Here, we combined experiment and theory to study near-surface swimming of flagellated bacteria in viscoelastic polymer fluids. In contrast to the swimming behavior in Newtonian fluids, we discovered that cells swim in less curved trajectories and display reduced near-surface accumulation. Using a theoretical analysis of the non-Newtonian hydrodynamic forces, we demonstrated the existence of a generic lift force acting on a rotating filament near a rigid surface, which arises from the elastic tension generated along curved flow streamlines. This viscoelastic lift force weakens the hydrodynamic interaction between flagellated swimmers and solid surfaces and contributes to a decrease in surface accumulation. Our findings reveal previously unrecognized facets of bacterial transport and surface exploration in polymer-rich environments that are pertinent to diverse microbial processes and may inform the design of artificial microswimmers capable of navigating through complex geometries.

Realizing the multifunctional metamaterial for fluid flow in a porous medium.

Metamaterials are artificial materials that can achieve unusual properties through unique structures. In particular, their "invisibility" property has attracted enormous attention due to its little or negligible disturbance to the background field that avoids detection. This invisibility feature is not only useful for the optical field, but it is also important for any field manipulation that requires minimum disturbance to the background, such as the flow field manipulation inside the human body. There are several conventional invisible metamaterial designs: a cloak can isolate the influence between the internal and external fields, a concentrator can concentrate the external field to form an intensified internal field, and a rotator can rotate the internal field by a specific angle with respect to the external field. However, a multifunctional invisible device that can continuously tune across all these functions has never been realized due to its challenging requirements on material properties. Inside a porous medium flow, however, we overcome these challenges and realize such a multifunctional metamaterial. Our hydrodynamic device can manipulate both the magnitude and the direction of the internal flow and, at the same time, make negligible disturbance to the external flow. Thus, we integrate the functions of the cloak, concentrator, and rotator within one single hydrodynamic metamaterial, and such metamaterials may find potential applications in biomedical areas such as tissue engineering and drug release.

Gender and Age Differences in the Evaluation and Clinical Outcomes of Patients with Palpitations.

BACKGROUND: Palpitations represent a common clinic complaint. OBJECTIVE: To explore gender and age differences in the evaluation and outcomes of patients with palpitations in outpatient settings. DESIGN/PARTICIPANTS: This is a retrospective observational study of 58,543 patients with no known structural cardiac disease or arrythmias presenting to primary care and cardiology clinics in an integrated health system in California with palpitations between January 2017 and December 2021. The primary and secondary endpoints were hospitalization for arrhythmia and all-cause mortality at 1 year. Multivariable logistic regression models evaluated the association between gender, age, and outcomes. RESULTS: Men and women were equally as likely to be started on beta-blockers (adjusted OR 0.96, 95% CI 0.90-1.02) and evaluated with electrocardiograms (adjusted OR 0.95, 95% CI 0.90-1.01) and cardiac monitors (adjusted OR 1.04, 95% CI 0.99-1.08). Patients who completed Holter or event monitors had a lower rate of hospitalization for cardiovascular disease at 1 year than those without (2.3% vs. 2.7%, p = 0.001). At 1 year, women had a lower risk of all-cause mortality (adjusted OR 0.47, 95% CI 0.35-0.64) and hospitalization for atrial fibrillation (adjusted OR 0.47, 95% CI 0.30-0.72) and arrhythmias (adjusted OR 0.73, 95% CI 0.58-0.91) compared to men. Among older women and men (≥ 80 years), there was no significant difference in 1-year all-cause mortality (adjusted OR 0.57, 95% CI 0.29-1.12), hospitalization for atrial fibrillation (adjusted OR 0.58, 95% CI 0.17-1.97), or arrhythmias (adjusted OR 1.15, 95% CI 0.12-11.07). CONCLUSIONS: There were no gender differences in referrals for cardiac monitoring or prescriptions for beta-blockers. Women had a better prognosis with a lower risk of hospitalization for arrhythmias and death at 1 year compared to men. However, 1-year risks for mortality and hospitalization for arrythmias among older women were comparable to those of older men, underscoring the importance of considering age and gender in managing patients with palpitations.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion.

Secondary amines, due to their reactivity, can transform protein templates into catalytically active entities, accelerating the development of artificial enzymes. However, existing methods, predominantly reliant on modified ligands or N-terminal prolines, impose significant limitations on template selection. In this study, genetic code expansion was used to break this boundary, enabling secondary amines to be incorporated into alternative proteins and positions of choice. Pyrrolysine analogues carrying different secondary amines could be incorporated into superfolder green fluorescent protein (sfGFP), multidrug-binding LmrR and nucleotide-binding dihydrofolate reductase (DHFR). Notably, the analogue containing a D-proline moiety demonstrated both proteolytic stability and catalytic activity, conferring LmrR and DHFR with the desired transfer hydrogenation activity. While the LmrR variants were confined to the biomimetic 1-benzyl-1,4-dihydronicotinamide (BNAH) as the hydride source, the optimal DHFR variant favorably used the pro-R hydride from NADPH for stereoselective reactions (e.r. up to 92 : 8), highlighting that a switch of protein template could broaden the nucleophile option for catalysis. Owing to the cofactor compatibility, the DHFR-based secondary amine catalysis could be integrated into an enzymatic recycling scheme. This established method shows substantial potential in enzyme design, applicable from studies on enzyme evolution to the development of new biocatalysts.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

A cost-effective, machine learning-based new unified risk-classification score (NU-CATS) for patients with endometrial cancer.

INTRODUCTION: Treatment for endometrial cancer (EC) is increasingly guided by molecular risk classifications. Here, we aimed at using machine learning (ML) to incorporate clinical and molecular risk factors to optimize risk assessment. METHODS: The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma (n = 596), Memorial Sloan Kettering-Metastatic Events and Tropisms (n = 1315) and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (n = 4561) datasets were used to identify genetic alterations and clinicopathological features. Software packages including Keras, Pytorch, and Scikit Learn were tested to build artificial neural networks (ANNs) with a binary output as either intra-abdominal metastatic progression ('1') vs. non-metastatic ('0'). RESULTS: Black patients with EC have worse prognosis than White patients, adjusting for TP53 or POLE mutation status. Over 75% of Black patients carry TP53 mutations as compared to approximately 40% of White patients. Older age is associated with an increasing likelihood of TP53 mutation, high risk histology, and distant metastasis. For patients above age 70, 91% of Black and 60% of White EC patients carry TP53 mutations. A ML-based New Unified classifiCATion Score (NU-CATS) that incorporates age, race, histology, mismatch repair status, and TP53 mutation status showed 75% accuracy in prognosticating intra-abdominal progression. A higher NU-CATS is associated with an increasing risk of having positive pelvic or para-aortic lymph nodes and distant metastasis. NU-CATS was shown to outperform Leiden/TransPORTEC model for estimating risk of FIGO Stage I/II disease progression and survival in Black EC patients. CONCLUSION: The NU-CATS, a ML-based, cost-effective algorithm, incorporates diverse clinicopathologic and molecular variables of EC and yields superior prognostication of the risk of nodal involvement, distant metastasis, disease progression, and overall survival.

Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case-control study.

BACKGROUND: The incidence of stroke is increasing among younger people with human immunodeficiency virus (HIV). The burden of stroke has shifted toward the young people living with HIV, particularly in low- and middle-income countries. People infected with herpes zoster (HZ) were more likely to suffer stroke than the general population. However, the association of HZ infection with the incidence of stroke among patients with HIV remains unclear. METHODS: A nested case-control study was conducted with patients with HIV registered in the Taiwan National Health Insurance Research Database in 2000-2017. A total of 509 stroke cases were 1:10 matched to 5090 non-stroke controls on age, sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% confidence intervals (CI) of stroke incidence. RESULTS: The odds ratio of stroke was significantly higher in the HIV-infected population with HZ (adjusted odds ratio [AOR]: 1.85, 95% CI: 1.42-2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86-4.34), heart disease (AOR: 2.32, 95% CI: 1.54-3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16-2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22-1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12-1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05-1.69). CONCLUSIONS: Our findings suggest that HZ concurrent with HIV may increase the risk of stroke. The incidence rates of stroke were independent of common risk factors, suggesting strategies for early prevention of HZ infection among people living with HIV.

Why does thionating a carbonyl molecule make it a better electron acceptor?

The past decade has witnessed a surge of biomedical and materials applications of thiocarbonyl molecules (R2CS), such as in photodynamic therapy, organic field-effect transistors, and rechargeable batteries. The success of these applications originates from thiocarbonyl's small optical gap in the visible region and the enhanced electron affinity compared to the carbonyl analogues (R2CO). Although these observations seem to be contrary to the implication based on a simple electronegativity consideration (2.58 for sulfur and 3.44 for oxygen), a natural bond orbital (NBO) analysis gives a straightforward explanation for the LUMO-lowering effect of CO → CS substitution. In comparison to the valence (2p)C/(2p)O interactions in CO, the higher 3p orbital of sulfur and its weaker overlap with the 2p level of carbon result in a weaker antibonding interaction in NBO, a prominent contributor to the LUMO. Such an analysis also provides a semi-quantitative understanding of the electronic effect of substituents on or in π-conjugation with a (thio)carbonyl functionality. The intuitive concepts uncovered here offer a simple rule to predict the electronic properties of π-conjugated molecules that incorporate heavy heteroelements and would facilitate materials development.

Weak synchronization and large-scale collective oscillation in dense bacterial suspensions.

Collective oscillatory behaviour is ubiquitous in nature, having a vital role in many biological processes from embryogenesis and organ development to pace-making in neuron networks. Elucidating the mechanisms that give rise to synchronization is essential to the understanding of biological self-organization. Collective oscillations in biological multicellular systems often arise from long-range coupling mediated by diffusive chemicals, by electrochemical mechanisms, or by biomechanical interaction between cells and their physical environment. In these examples, the phase of some oscillatory intracellular degree of freedom is synchronized. Here, in contrast, we report the discovery of a weak synchronization mechanism that does not require long-range coupling or inherent oscillation of individual cells. We find that millions of motile cells in dense bacterial suspensions can self-organize into highly robust collective oscillatory motion, while individual cells move in an erratic manner, without obvious periodic motion but with frequent, abrupt and random directional changes. So erratic are individual trajectories that uncovering the collective oscillations of our micrometre-sized cells requires individual velocities to be averaged over tens or hundreds of micrometres. On such large scales, the oscillations appear to be in phase and the mean position of cells typically describes a regular elliptic trajectory. We found that the phase of the oscillations is organized into a centimetre-scale travelling wave. We present a model of noisy self-propelled particles with strictly local interactions that accounts faithfully for our observations, suggesting that self-organized collective oscillatory motion results from spontaneous chiral and rotational symmetry breaking. These findings reveal a previously unseen type of long-range order in active matter systems (those in which energy is spent locally to produce non-random motion). This mechanism of collective oscillation may inspire new strategies to control the self-organization of active matter and swarming robots.

Dynamic motility selection drives population segregation in a bacterial swarm.

Population expansion in space, or range expansion, is widespread in nature and in clinical settings. Space competition among heterogeneous subpopulations during range expansion is essential to population ecology, and it may involve the interplay of multiple factors, primarily growth and motility of individuals. Structured microbial communities provide model systems to study space competition during range expansion. Here we use bacterial swarms to investigate how single-cell motility contributes to space competition among heterogeneous bacterial populations during range expansion. Our results revealed that motility heterogeneity can promote the spatial segregation of subpopulations via a dynamic motility selection process. The dynamic motility selection is enabled by speed-dependent persistence time bias of single-cell motion, which presumably arises from physical interaction between cells in a densely packed swarm. We further showed that the dynamic motility selection may contribute to collective drug tolerance of swarming colonies by segregating subpopulations with transient drug tolerance to the colony edge. Our results illustrate that motility heterogeneity, or "motility fitness," can play a greater role than growth rate fitness in determining the short-term spatial structure of expanding populations.

Toll-like receptor 10 expression in B cells is negatively correlated with the progression of primary Sjögren's disease.

Primary Sjögren's Disease (pSjD) is considered a B cell-mediated disease. Toll-like receptor 10 (TLR10) is highly expressed in human B cells, indicating that TLR10 probably plays a vital role in pSjD. We examined TLR10 expression in peripheral B subsets of pSjD patients and analyzed their association with disease activity. We observed that TLR10 expression in total, naïve, memory, and switched memory B cells was significantly increased in low-activity pSjD patients as compared with healthy controls and high-activity patients. TLR10 expression in the above mentioned B subsets (except naïve B) was negatively correlated with serum levels of anti-SSA antibody and BAFF, respectively. Moreover, a higher proportion of high-activity pSjD patients was observed in TLR10 low- than high-expressed patients. Our study concluded that TLR10 expression in CD19+ B and memory B was negatively correlated with pSjD disease activity, suggesting that TLR10 might take part in the progression of pSjD.

Suicidality Among People Living With HIV From 2010 to 2021: A Systematic Review and a Meta-regression.

OBJECTIVE: The association between human immunodeficiency virus (HIV)/AIDS and suicidality is not well understood, partly because of variability in results. This meta-analysis aimed to investigate the predictive value of HIV/acquired immune deficiency syndrome for incident suicidality. METHODS: A literature review was conducted of articles published between January 1, 2010, and October 31, 2021. The following databases were searched: Embase, MEDLINE, CINAHL, Web of Science, and Scopus. The search terms included human immunodeficiency virus (HIV), suicidal behavior, auto mutilation, and self-injurious behavior. Observational studies were screened following a registered protocol, and eligible ones were meta-analyzed and followed by meta-regression. RESULTS: A total of 43 studies were included in this systematic review, and a meta-regression included 170,234 participants. The pooled prevalence estimates of suicidal ideation, attempted suicide, and deaths by suicide were 22.3%, 9.6%, and 1.7%, respectively. The following significant risk factors for suicide ideation were found: substance use, depression, low quality of life, low social support, without HIV status disclosure, living alone, low level of memory problems, family history of suicide, and stage III of HIV. Risk factors for suicide attempts were depression and family history of suicide. An elevated risk for suicide-related death was found for people living with HIV (PLHIV) who had a psychiatric disorder and in studies conducted in hospital-based settings (versus national database studies or HIV clinic settings). CONCLUSIONS: The risk of suicidality is high among PLHIV within all six World Health Organization regions during the modern antiretroviral therapy era. Assessment of socioeconomic and psychological factors is recommended for further management to prevent suicide among PLHIV. The present findings are useful for design of intervention protocols and development of clinical practice guidelines intended to manage the well-being of PLHIV worldwide.

Time-domain convolution model for studying oscillation dynamics in an injection-locked optoelectronic oscillator.

A time-domain convolution model is proposed to study the oscillation dynamics in the injection-locked optoelectronic oscillator (OEO). The model has the ability to calculate multiple characteristics of the oscillation signal, such as the spectrum and the phase noise. Based on the model, the injection locking, the frequency pulling and the asymmetrical spectrum generation phenomena are numerically simulated in success. The simulation results fit in with the experimental results, indicating that the proposed model accurately describes the oscillation dynamics in the injection-locked OEO. In addition, the building-up process of the oscillation signal in the OEO is simulated. Alternating appearance of the sidebands on both sides of the primary oscillation mode is observed for the first time in the asymmetrical spectrum generation. This model is a powerful tool to study the oscillation dynamics in the injection-locked OEO.

γ-Secretase inhibitors suppress IL-20-mediated osteoclastogenesis via Notch signalling and are affected by Notch2 in vitro.

Rheumatoid arthritis (RA) is a chronic immune disease involving the small joints, which often causes irreversible damage. In recent years, elevated interleukin 20 (IL-20) has been observed in synovial fluid, while IL-20 receptor overexpression has been observed in synovial cells. IL-20 is a pleiotropic cytokine that participates in various immune diseases. Further understanding of the relationship between IL-20 and RA can help to identify a potential clinical treatment for RA. This study demonstrated that IL-20 can regulate osteoclast differentiation and function in a dose-dependent manner, while influencing the expression of Notch signalling. Quantitative reverse transcription polymerase chain reaction and western blotting showed that γ-secretase-inhibiting drugs can reverse the effects of IL-20. The effects of Notch2 on IL-20-induced osteoclastogenesis were investigated by immunofluorescence and Notch2 gene silencing via transfection of small interfering RNA; the results showed that Notch2 obviously affected the expression levels of the key protein NFATc1 and downstream osteoclastic proteins. In conclusion, we found that IL-20 regulated the osteoclastogenesis in a dose-dependent manner via Notch signalling, primarily by means of Notch2 activity. This study may help to find new targets for RA treatment.