Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits.

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFß mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation.

Position Adherence in Patients Underwent Pars Plana Vitrectomy with Silicone Oil Tamponade.

Introduction: Position adherence of patients with Pars Plana Vitrectomy with Silicone Oil Tamponade after discharge is of positive significance. However, patients undergoing a day surgery makes the quality of discharge teaching and readiness for hospital discharge is insufficient, which will influence their position adherence at home. Aim: This study aimed to find the correlation of discharge teaching, readiness for hospital discharge, and position adherence in patients who underwent PPV with silicone oil tamponade from the day ward. Methods: This was a cross-sectional survey. One hundred ninety-four patients with day surgery were recruited by convenient sampling from Zhongshan Ophthalmic Center, China. Data were collected using the quality of discharge teaching scale, readiness for hospital discharge scale, and position adherence scale. Results: Patients' education level, residence, poor postoperative vision, ophthalmic surgery history, and quality of discharge teaching are the main factors of readiness for discharge. Only 41(21%) patients had good position adherence, and education level and readiness for discharge are the main factors of position adherence. Discussion: Discharge teaching improves patients' knowledge and competence of self-care and helps patients prepare for the transition from hospital to home, and readiness for hospital discharge significantly influences position adherence after discharge and indirectly plays a vital role in postoperative vision recovery and surgical effect.

Engineering of Cerium Modified TiNb2O7 Nanoparticles For Low-Temperature Lithium-Ion Battery.

Although TiNb2O7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li4Ti5O12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li+ and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g-1 at 100 mA g-1 after 100 cycles, and 183.0 mA h g-1 even under 3200 mA g-1. In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g-1 can still reach 89.7 mA h g-1, corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature.

Spaced-Confined Janus Engineering Enables Controlled Ion Transport Channels and Accelerated Kinetics for Secondary Ion Batteries.

The large grain boundary resistance between different components of the anode electrode easily leads to the low ion transport efficiency and poor electrochemical performance of lithium-/sodium-ion batteries (LIBs/SIBs). To address the issue, a Janus heterointerface with a Mott-Schottky structure is proposed to optimize the interface atomic structure, weaken interatomic resistance, and improve ion transport kinetics. Herein, Janus Co/Co2P@carbon-nanotubes@core-shell (Janus Co/Co2P@CNT-CS) refined urchin-like architecture derived from metal-organic frameworks is reported via a coating-phosphating process, where the Janus Co/Co2P heterointerface nanoparticles are confined in carbon nanotubes and a core-shell polyhedron. Such a Janus Co/Co2P heterointerface shows the strong built-in electric field, facilitating the controllable ion transport channels and the high ion transport efficiency. The Janus Co/Co2P@CNT-CS refined urchin-like architecture composed of a core-shell structure and the grafting carbon nanotubes enhances the structure stability and electronic conductivity. Benefiting from the spaced-confined Janus heterointerface engineering and synergistic effects between the core-shell structure and the grafting carbon nanotubes, the Janus Co/Co2P@CNT-CS refined urchin-like architecture demonstrates the fast ion transport rate and excellent pseudocapacitance performance for LIBs/SIBs. In this case, the Janus Co/Co2P@CNT-CS refined urchin-like architecture shows high specific capacities of 709 mA h g-1 (200 cycles) and 203 mA h g-1 (300 cycles) at a current density of 500 mA g-1 for LIBs/SIBs, respectively.

Global, Regional, and National Epidemiology of Visual Impairment in Working-Age Individuals, 1990-2019.

Importance: Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective: To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants: This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure: Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures: Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results: There were 437 539 484 (95% uncertainty interval [UI], 325 463 851-575 573 588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228 530 964; 95% UI, 172 515 833-297 118 596). Over 3 decades, visual impairment-associated DALYs increased from 7 601 852 (95% UI, 5 047 030-11 107 897) to 12 563 276 (95% UI, 8 278 866-18 961 723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100 000 population in 2019 (26 008.45; 95% UI, 19 987.35-32 482.09), while South Sudan had the highest DALY rate per 100 000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance: Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.

Effectiveness of double ABCX-based psychotherapy for psychological distress among women undergoing in vitro fertilization-embryo transfer: a three-arm randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of double ABCX-based psychotherapy for psychological distress during in vitro fertilization-embryo transfer (IVF-ET) among a female group (FG), couple group (CoG) and control group (CG). METHODS: A total of 201 women undergoing their first IVF-ET cycle were randomized into three groups. The 6-session intervention was delivered at each visit to the IVF clinic. The primary outcomes were depression and anxiety, and the secondary outcomes included sleep quality, serum cortisol (nmol/L) levels and the clinical pregnancy rate, which were assessed before and after the intervention. RESULTS: The group-by-time effects were significant for depression, anxiety, sleep quality and serum cortisol levels, with larger effect sizes in the FG than in the CoG. There was no significant difference in the pregnancy rate among the three groups. CONCLUSION: Psychotherapy effectively mitigated psychological distress, suggesting greater effectiveness for couples undergoing IVF couples than for women only. It is structured and easy to use during the IVF treatment cycle. TRIAL REGISTRATION NUMBER: https://register.clinicaltrials.gov (NCT03931187, retrospectively registered on April 23, 2019).

Double ABCX-based psychotherapy, which was developed in this study, effectively mitigated depression, anxiety, sleep disturbance and increased cortisol levels, suggesting greater effectiveness for couples undergoing IVF-ET than women only.Double ABCX-based psychotherapy is structured and easy to use during the IVF-ET treatment cycle, thereby presenting a promising and feasible approach to improve care for couples or women with assisted reproductive technique-related stress.

Effect of particles size of TiC on oxidation resistance of in-situ TiC/Ni composite.

The oxidation resistance of TiC/Ni composites is crucial for its application in high-temperature oxidation environment. The in-situ TiC/Ni composites are fabricated by reactive sintering method, and the influence of TiC particle size on oxidation resistance of composite is studied. The particle size of TiC increases from 1.54 µm to 2.40 µm as the sintering holding time prolongs from 2 h to 6 h, due to the dissolution-reprecipitation mechanism. The oxidation kinetics of in-situ TiC/Ni composite with different TiC particle size oxidized at 800 °C for 100 h obeys parabolic kinetics. The oxidation mass gain of composite increases from 7.471 mg•cm-2 to 8.454 mg•cm-2, and the oxide scale on composites becomes thicker, as the particle size of TiC increases from 1.54 µm to 2.40 µm. The reduction of TiC particle size facilitates the formation of a dense and continuous oxide scale on composite, helpful to restrict the diffusion of O, Ti and Ni atoms during oxidation. Therefore, the reduction of TiC particle size is contributed to the optimization of oxidation resistance of in-situ TiC/Ni composites.

Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1.

Hair follicle (HF) growth and development are controlled by various cell types, including hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Exosomes are nanostructures that participate in many biological processes. Accumulating evidence indicates that DPC-derived exosomes (DPC-Exos) mediate HFSC proliferation and differentiation during the cyclical growth of hair follicles. In this study, we found that DPC-Exos increase ki67 expression and CCK8 cell viability readouts in HFSCs but reduce annexin staining of apoptotic cells. RNA sequencing of DPC-Exos-treated HFSCs identified 3702 significantly differentially expressed genes (DEGs), including BMP4, LEF1, IGF1R, TGFß3, TGFα, and KRT17. These DEGs were enriched in HF growth- and development-related pathways. We further verified the function of LEF1 and showed that overexpression of LEF1 increased the expression of HF development-related genes and proteins, enhanced HFSC proliferation, and reduced HFSC apoptosis, while knockdown of LEF1 reversed these effects. DPC-Exos could also rescue the siRNA-LEF1 effect in HFSCs. In conclusion, this study demonstrates that DPC-Exos mediated cell-to-cell communication can regulate HFSCs proliferation by stimulating LEF1 and provide novel insights into HF growth and development regulatory mechanisms.

The role of remote sensing during a global disaster: COVID-19 pandemic as case study.

Remotely sensed imagery is used as a tool to aid decision makers and scientists in a variety of fields. A recent world event in which satellite imagery was extensively relied on by a variety of stakeholders was the COVID-19 pandemic. In this article we aim to give an overview of the types of information offered through remote sensing (RS) to help address different issues related to the pandemic. We also discuss about the stakeholders that benefited from the data, and the value added by its availability. The content is presented under four sub-sections; namely (1) the use of RS in real-time decision-making and strategic planning during the pandemic; how RS revealed the (2) environmental changes and (3) social and economic impacts caused by the pandemic. And (4) how RS informed our understanding of the epidemiology of SARS-CoV-2, the pathogen responsible for the pandemic. High resolution optical imagery offered updated on-the-ground data for e.g., humanitarian aid organizations, and informed operational decision making of shipping companies. Change in the intensity of air and water pollution after reduced anthropogenic activities around the world were captured by remote sensing - supplying concrete evidence that can help inform improved environmental policy. Several economic indicators were measured from satellite imagery, showing the spatiotemporal component of economic impacts caused by the global pandemic. Finally, satellite based meteorological data supported epidemiological studies of environmental disease determinants. The varied use of remote sensing during the COVID-19 pandemic affirms the value of this technology to society, especially in times of large-scale disasters.

Subtypes of work engagement in frontline supporting nurses during COVID-19 pandemic: A latent profile analysis.

AIM: The aim was to examine the subgroups of work engagement in frontline nurses during the COVID-19 pandemic. BACKGROUND: The pandemic may affect the work engagement of nurses who have direct contact with infected patients and lead to a poor quality of care. Identifying classification features of work engagement and tailoring interventions to support frontline nurses is imperative. DESIGN: This study utilized a cross-sectional study design. METHODS: Three hundred fifty-five nurses were enrolled in this cross-sectional study from 14 February to 15 April 2020. A latent profile analysis was performed to identify classification features of work engagement. Multiple logistic regression analyses were used to examine predictors of profile membership. RESULTS: A four-profile model provided the best fit. The four profiles were titled 'low work engagement' (n = 99), 'high vigour-low dedication and absorption' (n = 58), 'moderate work engagement' (n = 63) and 'high work engagement' (n = 135). A regression analysis suggested that young nurses and nurses who were the only children of their family were more likely to be in the 'low work engagement' and 'high vigour-low dedication and absorption' groups. CONCLUSION: This study highlights the importance of tailoring interventions for frontline supporting nurses by considering their distinct work engagement patterns, especially during the COVID-19 pandemic, to improve the promotion of work satisfaction and quality of care. IMPACT: This was the first study to explore the latent profiles of work engagement in frontline nurses during the COVID-19 pandemic. Over 40% of nurses were in the 'low work engagement' and 'high vigour-low dedication and absorption' groups and reported low levels of work engagement. Understanding different patterns of work engagement in frontline nurses can help nursing managers provide emotional, material and organizational support based on the features of each latent profile, which may improve the quality of care and patient safety.

Associated risk factors of postoperative pain after glaucoma surgery: a prospective study.

PURPOSE: This study aimed to determine degree of postoperative pain and the incidence of serious postoperative pain after glaucoma surgery and further to identify the associated risk factors. METHODS: A total of 194 consecutive patients who were diagnosed with glaucoma and underwent glaucoma surgery were enrolled in this study. The intensity of postoperative pain was evaluated using numerical rating scale (NRS) within 24 h after surgery; NRS ≥ 5 was considered as clinically significant postoperative pain. Risk factors associated with the development of postoperative pain were analyzed by multivariate logistic regression analysis. RESULTS: Clinically significant postoperative pain was experienced at any time after glaucoma surgery in 41.75% of the patients, which peak at 2 h. 27.8% of the patients requested analgesic medication within 24 h after surgery. According to multivariate logistic regression analysis, preoperative anxiety (OR = 4.13 [1.29-13.2], p = 0.017), cyclophotocoagulation (OR = 30.9 [3.47-375.1], p = 0.002), and phacotrabeculectomy combined with or without intraocular lens implantation (OR = 30.0 [2.69-335.6], p = 0.006) were associated with increased clinically significant postoperative pain. Interestingly, patients with diabetes and/or hypertension were associated with less postoperative pain after glaucoma surgery (OR = 0.23 [0.08-0.64], p = 0.005). CONCLUSION: Patients undergoing glaucoma surgery tend to experience postoperative pain in the early postoperative period. Anxiety level and surgery types of cyclophotocoagulation and phacotrabeculectomy are risk factors for postoperative pain. Patients with diabetes and/or hypertension are less likely to develop postoperative pain.

Exploring the Role of Social Support between Discharge Teaching and Readiness for Discharge in Ocular Fundus Disease Patients: A Cross-Sectional Study.

BACKGROUND: This study aims to evaluate the quality of discharge teaching and readiness for discharge of fundus disease patients treated with day surgery and understand the role of social support between them. METHODS: This was a cross-sectional descriptive correlational survey. Through convenient sampling, fundus disease patients treated with day surgery from Zhongshan Ophthalmic Center, China, were recruited. Data were collected using demographic and disease-related information, quality of discharge teaching scale, readiness for hospital discharge scale, and social support scale. RESULTS: 255 fundus disease patients treated with day surgery were recruited at last. The mean total score of readiness for discharge, quality of discharge teaching, and social support in patients with fundus disease were 157.91 (SD = 26.68), 122.97 (SD = 21.55), and 36.32 (SD = 7.60), respectively. Participants with stronger social support had better discharge teaching and then had higher readiness for discharge. Social support played a partial mediator role in the relationship between discharge teaching and readiness for discharge. The mediation effect ratio was 5.5%. CONCLUSIONS: The quality of discharge teaching and social support among fundus disease patients who underwent day surgery was relatively high, and readiness for discharge was good. Social support is essential for the quality of discharge teaching and the improvement of discharge readiness. Clinical nurses need to provide appropriate guidelines to help patients seek effective support and improve quality of discharge teaching to enhance the readiness for discharge of fundus disease patients treated with day surgery.

[Mediation role of self-efficacy between social support and depression of only-child-lost people].

OBJECTIVE: To investigate the relationship between social support and depression of only-child-lost (OCL) people, and the mediation role of self-efficacy in this relationship. 
 Methods: By stratified cluster sampling, 214 OCL people were enrolled, with 80 males and 134 females, ages from 49 to 83 years old. They were assessed by General Self-Efficacy Scale, Social Support Rating Scale, and Self-rating Depression Scale.
 Results: Univariate analysis showed that there were significant differences in age groups (t=2.85, P<0.05), with or without spouse (t=5.62, P<0.05), family location (t=3.95, P<0.05), per capita monthly income (F=3.48, P<0.05) among the social support scores. There was significant difference between the per capita monthly income and self-efficacy scores in QCL people (F=5.46, P<0.05). Correlation analysis showed self-efficacy and social support were positively correlated (r=0.26, P<0.01). Self-efficacy (r=-0.59, P<0.01) and social support (r=-0.59, P<0.01) negatively correlated with depression in OCL people. Self-efficacy partially mediated the relationship between social support and depression.
 Conclusion: The person who is <60 years old, with spouse and the high per capita monthly income, and lives the rural area, would have high social support levels among QCL people. The person who has high per capita monthly income would have high self-efficacy. Self-efficacy is one of the direct prediction for depression, and plays an indirect role between social support and depression. Intervention of depression among OCL people could be applied to change their cognition, and to enhance their self-efficacy.

Latent classes of resilience and psychological response among only-child loss parents in China.

Only-child loss parents in China recently gained extensive attention as a newly defined social group. Resilience could be a probable solution out of the psychological dilemma. Using a sample of 185 only-child loss people, this study employed latent class analysis (a) to explore whether different classes of resilience could be identified, (b) to determine socio-demographic characteristics of each class, and (c) to compare the depression and the subjective well-being of each class. The results supported a three-class solution, defined as 'high tenacity-strength but moderate optimism class', 'moderate resilience but low self-efficacy class' and 'low tenacity but moderate adaption-dependence class'. Parents with low income and medical insurance of low reimbursement type and without endowment insurance occupied more proportions in the latter two classes. The latter two classes also had a significant higher depression scores and lower subjective well-being scores than high tenacity-strength but moderate optimism class. Future work should care those socio-economically vulnerable bereaved parents, and an elastic economic assistance policy was needed. To develop targeted resilience interventions, the emphasis of high tenacity-strength but moderate optimism class should be the optimism. Moderate resilience but low self-efficacy class should be self-efficacy, and low tenacity but moderate adaption-dependence class should be tenacity.

Latent Profiles of Posttraumatic Growth and Their Relation to Differences in Resilience among Only-Child-Lost People in China.

AIMS: Since the early 1980s, the one-child policy has been implemented nationwide in China. A special group called the "only-child-lost family" (OCL family) has emerged and has become a social phenomenon that cannot be ignored. We report latent profiles of posttraumatic growth and their relation to differences in resilience among OCL people in China. METHODS: A total of 222 OCL people were investigated using the Posttraumatic Growth Inventory and the Connor-Davidson Resilience Scale. Latent profile analysis was applied to explore PTG latent profiles. Multinomial logistic regression was used to analyze the socio-demographic variables in each latent profile and the association between profile membership and resilience. RESULTS: Three latent profiles were identified and labeled the "high appreciation-power group" (30.6%), the "general moderate growth group" (47.7%) and the "low growth and extreme possibility group" (21.7%). Compared to those in the high appreciation-power group, individuals with monthly income >2000 ($312) were less likely to be in the general moderate growth group (OR = 0.13, P<0.01), whereas individuals with a spouse were less likely to be in the low growth and extreme possibility group (OR = 0.43, P<0.01). Individuals in the "general moderate growth group"(OR = 0.92, P<0.01, 95%CI:0.89-0.94) and the "low growth and extreme possibility" groups (OR = 0.83, P<0.01, 95%CI:0.79-0.87) demonstrated significantly lower levels of resilience compared to the high appreciation-power group. CONCLUSION: The PTG patterns in only-child-lost parents were varied. Promoting resilience may be a way to foster these parents' PTG. Targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to the mental health of OCL parents who are without a spouse and have low income.

Type I IFN signaling facilitates the development of IL-10-producing effector CD8+ T cells during murine influenza virus infection.

Recent evidence has suggested that IL-10-producing effector CD8+ T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8+ T cells are not completely defined. Here, we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8+ T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung APCs, thereby facilitating IL-10-producing CD8+ T-cell development through a CD8+ T-cell-nonautonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T cells is required for the maximal generation of IL-10-producing CD8+ T cells. Type I IFN signaling in CD8+ T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4) and B-lymphocyte-induced maturation protein-1 (Blimp-1), two transcription factors required for the production of IL-10 by effector CD8+ T cells. Our data reveal a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+ T cells during respiratory virus infection.

[Knowledge and attitude of clinical interns on pain management].

OBJECTIVE: To investigate clinical interns' knowledge and attitude on pain management, influential factors and requirement.
 METHODS: A total of 212 clinical interns were investigated by the self-designed general condition questionnaire and the Chinese version of the knowledge and attitude survey regarding pain (KASRP).
 RESULTS: The correct answer rate for the knowledge and attitude questionnaire was (51.70±14.18)%. The education background, the condition of pain education in clinical practice and the use of pain assessment tools were the key factors that impact the scores of knowledge and attitude on pain management.
 CONCLUSION: Clinical interns' perception on pain management is insufficient. It cannot meet the clinical actual needs. The medical colleges are lack of pain management education courses and standardization training. Schools and hospitals are encouraged to offer and strengthen pain education for clinical interns to create a good environment for pain treatment and to improve the management level for patients' quality of life.

Activation of dendritic cell function by soypeptide lunasin as a novel vaccine adjuvant.

The addition of an appropriate adjuvant that activates the innate immunity is essential to subsequent development of the adaptive immunity specific to the vaccine antigens. Thus, any innovation capable of improving the immune responses may lead to a more efficacious vaccine. We recently identified a novel immune modulator using a naturally occurring seed peptide called lunasin. Lunasin was originally isolated from soybeans, and it is a small peptide containing 43 amino acids. Our studies revealed stimulatory effects of lunasin on innate immune cells by regulating expression of a number of genes that are important for immune responses. The objective was to define the effectiveness of lunasin as an adjuvant that enhances immune responses. The immune modulating functions of lunasin were characterized in dendritic cells (DCs) from human peripheral blood mononuclear cells (PBMCs). Lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when comparing with medium control treatment in the mixed leukocyte reaction (MLR). Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA-expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells. In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the MHC class I OVA peptide SIINFEKL (PR8-OTI). These results suggest that lunasin may function as a vaccine adjuvant by promoting DC maturation, which in turn enhances the development of protective immune responses to the vaccine antigens.

CD4+ T cells contain early extrapulmonary tuberculosis (TB) dissemination and rapid TB progression and sustain multieffector functions of CD8+ T and CD3- lymphocytes: mechanisms of CD4+ T cell immunity.

The possibility that CD4(+) T cells can act as "innate-like" cells to contain very early Mycobacterium tuberculosis dissemination and function as master helpers to sustain multiple effector functions of CD8(+) T cells and CD3(-) lymphocytes during development of adaptive immunity against primary tuberculosis (TB) has not been demonstrated. We showed that pulmonary M. tuberculosis infection of CD4-depleted macaques surprisingly led to very early extrapulmonary M. tuberculosis dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. CD4 depletion during M. tuberculosis infection revealed the ability of CD8(+) T cells to compensate and rapidly differentiate to Th17-like/Th1-like and cytotoxic-like effectors, but these effector functions were subsequently unsustainable due to CD4 deficiency. Whereas CD3(-) non-T lymphocytes in the presence of CD4(+) T cells developed predominant Th22-like and NK-like (perforin production) responses to M. tuberculosis infection, CD4 depletion abrogated these Th22-/NK-like effector functions and favored IL-17 production by CD3(-) lymphocytes. CD4-depleted macaques exhibited no or few pulmonary T effector cells constitutively producing IFN-γ, TNF-α, IL-17, IL-22, and perforin at the endpoint of more severe TB, but they presented pulmonary IL-4(+) T effectors. TB granulomas in CD4-depleted macaques contained fewer IL-22(+) and perforin(+) cells despite the presence of IL-17(+) and IL-4(+) cells. These results implicate a previously unknown innate-like ability of CD4(+) T cells to contain extrapulmonary M. tuberculosis dissemination at very early stage. Data also suggest that CD4(+) T cells are required to sustain multiple effector functions of CD8(+) T cells and CD3(-) lymphocytes and to prevent rapid TB progression during M. tuberculosis infection of nonhuman primates.

Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation.

Upon infection, CD8(+) T cells undergo a stepwise process of early activation, expansion, and differentiation into effector cells. How these phases are transcriptionally regulated is incompletely defined. Here, we report that interferon regulatory factor 4 (IRF4), dispensable for early CD8(+) T cell activation, was vital for sustaining the expansion and effector differentiation of CD8(+) T cells. Mechanistically, IRF4 promoted the expression and function of Blimp1 and T-bet, two transcription factors required for CD8(+) T cell effector differentiation, and simultaneously repressed genes that mediate cell cycle arrest and apoptosis. Selective ablation of Irf4 in peripheral CD8(+) T cells impaired antiviral CD8(+) T cell responses, viral clearance, and CD8(+) T cell-mediated host recovery from influenza infection. IRF4 expression was regulated by T cell receptor (TCR) signaling strength via mammalian target of rapamycin (mTOR). Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responses.