Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia.

BACKGROUND: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents. METHODS: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant. Arterial ligation or wire injury was used to induce neointima in mice, whereas ApoE-/- and LDLR-/- (LDLR [low-density lipoprotein receptor]) mice fed a high-fat diet were applied to assess atherosclerosis. In addition, coronary stent implantation was performed on vaccine-immunized Bama miniature pigs, followed by optical coherence tomography to evaluate coronary intimal hyperplasia. RESULTS: A vaccine, ATS7vac, was screened out from 3 candidates to effectively inhibit intimal thickening in murine carotid artery ligation models after vaccination. As well, immunization with ATS7vac alleviated neointima formation in murine wire injury models and mitigated atherosclerotic lesions in both hyperlipidemic ApoE-/- and LDLR-/- mice without lowering lipid levels. Preclinically, ATS7vac markedly impeded intimal hyperplasia in swine stented coronary arteries, but without significant immune-related organ injuries. Mechanistically, ATS7vac vaccination produced specific antibodies against ADAMTS-7, which markedly repressed ADAMTS-7-mediated COMP (cartilage oligomeric matrix protein) and TSP-1 (thrombospondin-1) degradation and subsequently inhibited vascular smooth muscle cell migration but promoted re-endothelialization. CONCLUSIONS: ATS7vac is a novel atherosclerosis vaccine that also alleviates in-stent restenosis. The application of ATS7vac would be a complementary therapeutic avenue to the current lipid-lowering strategy for atherosclerotic disease.

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Unequal Health Risks and Attributable Mortality Burden of Source-Specific PM2.5 in China.

Anthropogenic emissions, originating from human activities, stand as the primary contributors to PM2.5, which is recognized as a global health threat. The disease burden associated with PM2.5 has been extensively documented. However, the prevailing estimations have predominantly relied on PM2.5 exposure-response functions, neglecting the distinct risks posed by PM2.5 from various sources. China has experienced a significant reduction in the PM2.5 concentration due to stringent emission controls. With diverse sources and abundant mortality data, this situation provides a unique opportunity to estimate short-term source-specific attributable mortality. Our approach involves an integrated unequal health risk-oriented modeling in China, incorporating a source-oriented Community Multiscale Air Quality model, an adjustment and downscaling method for exposure measurement, a generalized linear model with random-effects meta-analysis, and premature mortality estimation. Adhering to the unequal health risk concept, we calculated the attributable mortality of multiple PM2.5 sources by determining the source risk-adjusted factor. In this study, we observed varying excess risks associated with multiple PM2.5 sources, with transportation-related PM2.5 exhibiting the most substantial association. An interquartile range increase (7.65 µg/m3) was linked to a 1.98% higher daily nonaccidental mortality. Residential use- and transportation-related PM2.5 emerged as the two principal sources of premature mortality. In 2018, a remarkable 53,381 avoiding deaths were estimated compared to 2013, and over 67% of these were attributed to reductions in coal-dependent sources. Notably, transportation-related PM2.5 emerged as the largest contributor to premature mortality in 2018. This study underscores the significance of a new source-oriented health risk assessment to support actions aimed at reducing air pollution. It strongly advocates for heightened attention to PM2.5 reductions in the transportation sector in China.

Continued Rise in Health Burden from Ambient PM2.5 in India under SSP Scenarios Until 2100 despite Decreasing Concentrations.

Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.

Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Schadenfreude or empathy? Children's emotional responses to the physical pain and pleasure of prosocial and antisocial others.

Adults' emotional reactions to the pain and pleasure of others are influenced by the moral character of those individuals. However, it remains unclear whether children's emotional responses also show such selectivity. To investigate this, we compared 4- to 8-year-old children's emotional responses to the physical pain and pleasure of prosocial versus antisocial puppets. In Study 1, children reported unhappiness after witnessing the pain of the prosocial and antisocial puppets but reported less unhappiness after witnessing the pain of the antisocial puppet. In Study 2, children reported happiness after witnessing the pleasure of both puppets but reported being less happy for the antisocial puppet. These results suggest that children are less likely to empathize with antisocial individuals. Meanwhile, children did not display Schadenfreude (pleasure at others' pain) or Gluckschmerz (displeasure at others' pleasure) toward antisocial individuals in our studies. Moreover, the selectivity of children's emotional responses disappeared after we manipulated the physical competence rather than the moral character of the puppets in Study 3. Our findings help to reveal the moral selectivity of emotional responses to others' pleasure and pain during early childhood.

Leaf Spot caused by Alternaria tenuissima on Rhamnella franguloides in China.

The small tree species Rhamnella franguloides, belonging to the genus Rhamnella in the tribe Rhamneae Hook. f. of Rhamnaceae (Hauenschild et al. 2016), is an important medicinal plant commonly used for making tea in China. In August 2023, leaf spot symptoms were observed on R. franguloides in Shangyao county, Yantai, Shandong, China, with a disease incidence of 45-65%. Initially appearing as small dark brown spots on the tip lesions, they later expanded and merged into irregular-shaped brown necrotic lesions with yellowish halos. To isolate pathogen, 20 symptomatic tissue fragments (5 × 5 mm) from ten sampling randomly plants were surface sterilized, placed on potato dextrose agar (PDA) plates, and incubated at 25°C in darkness for 3 days to obtain colonies.10 purified isolates with similar morphological characteristics were obtained by single-spore isolation from the colonies. The representative isolate MR13 was chosen for morphological and molecular analysis. The colonies On PDA medium initially appear as a circular yellow-brown ring with white round margins, ultimately turning into olive green with fluffy aerial hyphae. The conidiophores displayed brown pigmentation, solitary or branched, producing abundant short chains of conidia. The conidia were typically obclavate to obpyriform or ellipsoid in shape, 22.5-64.5 × 12.5-23.6µm in size, with a short conical beak at the apex, zero to three longitudinal septa and one to five transverse septa. Based on cultural and morphological characteristics, the fungus was identified as Alternaria spp (Simmons 2007). Due to morphological traits, five genes (the internal transcribed spacer [ITS], actin [ACT], plasma membrane ATPase [ATP], Alternaria major allergen [Alt a1] and histone 3 [H3]) form MR13 were amplified using primer pairs ITSI / ITS4, ACTDF1/R1, ATPDF1 / ATPDRI, Alt-for / Alt-rev, and H3-1a/1b, respectively (Hong et al. 2005; Lawrence et al. 2013; Lousie and Donaldson 1995). BLASTn analysis failed to confirm the identification of MR13 species based on ITS, ACT, ATP and Alt a1(ITS, OR668512; ACT, OR676918; ATP, OR676917; Alt a1, OR676919). The phylogenetic tree showed that it was closely related to Alternaria alternate, A. tenuissima, and A. destruens. The H3 sequence (OR676920) exhibited 100% similarity to A. tenuissima (OR485421). The phylogenetic tree constructed solely with H3 further confirmed MR13 as A. tenuissima. Pathogenicity tests were conducted by introducing the fungus onto healthy R. franguloides leaves in the field. Fifty leaves (five per plant) were treated with a 20ml suspension containing around 1x10^4 spores/ml, while an equal number of control samples were sprayed with distilled water. Transparent plastic bags were used to cover the treated leaves for 48 hours and maintain humidity. After fourteen days of inoculation, consistent leaf spotting symptoms were observed. In contrast, the control leaves showed no sign of infection. The fungal pathogen was successfully reisolated and identified as A. tenuissima through morphological and sequence analysis, fulfilling Koch's postulates. To our knowledge, this is the first report of A. tenuissima causing leaf spot disease on R. franguloides in China. Identifying the disease's causal agent is crucial for developing effective management strategies.

Ultrasound-based detection of inflammatory changes for early diagnosis and risk model construction of psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavorable health outcomes. The application of ultrasound enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed ultrasound models to aid early diagnosis of PsA. METHODS: This is a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough ultrasound examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45) and over 45 group (age > 45) and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were performed for model verification. RESULTS: A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and sixteen independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95%CI: 0.78-0.87) and 0.83 (95%CI: 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. CONCLUSION: The implementation of the ultrasound models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.

Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis.

OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis.

BACKGROUND: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. METHODS: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. RESULTS: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. CONCLUSIONS: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Exploring Health Effects under Specific Causes of Mortality Based on 90 Definitions of PM2.5 and Cold Spell Combined Exposure in Shanghai, China.

In this study, a total of 90 definitions were set up based on six air pollution definitions, five cold spell definitions, and three combined exposure scenarios. The relative risks (RRs) on all-cause, circulatory, and respiratory mortality were explored by a model combining a distributed linear lag model with quasi-Poisson regression. The definition in which daily PM2.5 increases more than 75 µg/m3 for at least 2 days and the average temperature falls below the 10th percentile for at least 2 days produced the best model fit performance in all-cause mortality. The high peaks of the health effect were generally observed around the lag days 6-9. The cumulative relative risks (CRRs) were more significant in the simultaneous-exposure scenario and higher in respiratory mortality, where the highest CRR (12.15, 3.69-40.03) was observed in definition P1T5, in which daily PM2.5 increases more than 75 µg/m3, and the average temperature falls below the 2.5th percentile for at least two days. For relative risk due to interaction (RERI), we found positive additive interactions (RERI > 0) between PM2.5 pollution and cold spell, especially in respiratory mortality. Clarifying the definition of combined events can help policymakers to capture health risks and construct more effective risk warning systems.

The relation between aggression and theory of mind in children: A meta-analysis.

Previous findings on the association between theory of mind (ToM) and aggression in children are mixed. The social skills deficit view regarded ToM as a single-edged sword and proposed that a lack of ToM can lead to aggression, while the double-edged sword view proposed that children with advanced ToM can still show much aggression because children can also leverage ToM to harm others. To resolve the dispute between the two views, we conducted a meta-analysis combining cross-sectional and longitudinal findings from 53 studies including a total of 11,579 children aged between 2 and 15 years. The overall negative correlation between ToM and aggression was small but significant (r = -0.08). The negative correlation was robust, with the magnitude of the correlation being similar across physical versus relational aggression, proactive versus reactive aggression, cognitive versus affective ToM, preschoolers versus school-aged children, different aggression measurements, and different levels of societal individualism. Moreover, the negative correlation was found regardless of whether ToM and aggression were measured concurrently or at different time points, but the correlation was the largest when ToM was measured before aggression. Whether the aggression was bullying or not also moderated the association, with ToM only being negatively related to non-bullying aggression but not bullying. Together, these findings suggest that ToM is a single-edged sword to decrease general aggression and that aggression might also give rise to lower ToM capacity during development. RESEARCH HIGHLIGHTS: This study systemically reviewed the existing mixed findings on the association between aggression and ToM during childhood using a meta-analysis. There was a negative correlation between ToM and aggression in children aged between 2 and 15 years. The negative correlation between aggression and ToM was stronger when ToM was measured first, followed by aggression, than vice versa. There was a negative correlation between non-bullying aggression and ToM, whereas there was no correlation between bullying and ToM.

Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.

This study was to investigate the relationship between the levels of Angiopoietin-Like Protein 4 (ANGPTL4) and Silent Mating-type Information Regulation 2 Homolog 1 (SIRT1) and the stability of carotid atherosclerotic plaque. For this purpose, 108 patients with coronary heart disease in our hospital from Jan 2021 to May 2022 were selected as the coronary heart disease (CHD) group and 80 patients with the healthy examination as the control group. Patients' serum levels of ANGPTL4 and SIRT1 were collected, and their stability of carotid atherosclerotic plaque was determined by carotid ultrasound. According to their stability results, patients were divided into three subgroups: No plaque, Stable plaque, and Unstable plaque. The serum ANGPTL4 and SIRT1 levels were analyzed in different groups, and the correlation between their serum levels and the stability of carotid atherosclerotic plaque was analyzed by rank correlation. Results showed that the CHD group's serum ANGPTL4 and SIRT1 levels were lower, with statistical significance (P<0.05); A statistically significant difference in serum ANGPTL4 and SIRT1 levels were observed among patients with No plaques, Stable plaques, and Unstable plaques (P<0.05); A negative correlation was observed between serum levels of ANGPTL4 and SIRT1 and the stability of carotid atherosclerotic plaque (r=-0.438, -0.717, P<0.001); Serum ANGPTL4 and SIRT1 can be used as the evaluation method of carotid atherosclerotic plaque stability. When ANGPTL4 ≤ 30.17mg/L and SIRT1 ≤ 6.91µg/L, patients were more likely to develop unstable plaques; When ANGPTL4 ≤ 30.40mg/L and SIRT1 ≤ 6.87µg/L, patients were more likely to develop plaques (instability and/or stability). In conclusion, the serum levels of ANGPTL4 and SIRT1 in patients with CHD decreased. ANGPTL4 and SIRT1 will participate in the formation and development of carotid plaque, which can be used as a serological evaluation index to evaluate the occurrence and carotid atherosclerotic plaque's stability.

Case Report: Multimodal, Longitudinal Assessment of Retinal Structure and Function following Laser Retinal Injury.

SIGNIFICANCE: This case report demonstrates the use of novel imaging techniques and functional tests to longitudinally evaluate retinal structure and function after laser retinal injury. The structural and functional prognosis could be predicted with clinical findings, high-resolution retinal imaging, and functional testing. PURPOSE: We present a laser retinal injury case in which an adaptive optics scanning laser ophthalmoscope and adaptive optics-based psychophysics were used to examine and monitor retinal structure and function after accidental exposure to a 1-W infrared laser beam. CASE REPORT: A 23-year-old patient was unwittingly exposed to a 1-W, 852-nm continuous-wave laser at work as they noticed a small central blurry spot in the right eye. An initial eye examination was done 1 day after exposure, and the right eye's acuity was 20/25 -2 . Posterior segment evaluation revealed disrupted outer retina near the right eye's fovea. Adaptive optics imaging 2 weeks after the exposure revealed a 0.50 × 0.75° elliptical area with irregular borders and abnormal cone reflectivity just below the fovea. Starting at 1-month follow-up, structural recovery was observed on optical coherence tomography (OCT). Subsequent adaptive optics imaging showed significant recovery of cone reflectivity. Importantly, adaptive optics microperimetry showed measurable detection thresholds at all affected retinal locations at 6 months. By 10 months, all sites exhibited normal sensitivities. CONCLUSIONS: Retinal structure and function from laser injury can be visualized and measured with OCT, adaptive optics imaging, and psychophysics. An intact Bruch's membrane on OCT and measurable retinal sensitivity by adaptive optics microperimetry may serve as good biomarkers for retinal recovery.

Enhanced S-cone Syndrome, a Mini-review.

Enhanced S-cone Syndrome (ESCS) is an autosomal recessive inherited retinal disease mostly associated with disease-causing variants in the NR2E3 gene. During retinal development in ESCS, rod photoreceptor precursors are misdirected to form photoreceptors similar to short-wavelength cones, or S-cones. Compared to a normal human retina, patients with ESCS have no rods and significantly increased numbers of S-cones. Night blindness is the main visual symptom, and visual acuity and color vision can be normal at early disease stages. Histology of donor eyes and adaptive optics imaging revealed increased S-cone density outside of the fovea compared to normal. Visual function testing reveals absent rod function and abnormally enhanced sensitivity to short-wavelength light. Unlike most retinal degenerative diseases, ESCS results in a gain in S-cone photoreceptor function. Research involving ESCS could improve understanding of this rare retinal condition and also shed light on the role of NR2E3 expression in photoreceptor survival.

Structure Engineering of BiSbSx Nanocrystals Embedded within Sulfurized Polyacrylonitrile Fibers for High Performance of Potassium-Ion Batteries.

Potassium-ion batteries (PIBs) are regarded as promising candidates in next-generation energy storage technology; however, the electrode materials in PIBs are usually restricted by the shortcomings of large volume expansion and poor cycling stability stemming from a high resistance towards diffusion and insertion of large-sized K ions. In this study, BiSbSx nanocrystals are rationally integrated with sulfurized polyacrylonitrile (SPAN) fibres through electrospinning technology with an annealing process. Such a unique structure, in which BiSbSx nanocrystals are embedded inside the SPAN fibre, affords multiple binding sites and a short diffusion length for K+ to realize fast kinetics. In addition, the molecular structure of SPAN features robust chemical interactions for stationary diffluent discharge products. Thus, the electrode demonstrates a superior potassium storage performance with an excellent reversible capacity of 790 mAh g-1 (at 0.1 A g-1 after 50 cycles) and 472 mAh g-1 (at 1 A g-1 after 2000 cycles). It's one of the best performances for metal dichalcogenides anodes for PIBs to date. The unusual performance of the BiSbSx @SPAN composite is attributed to the synergistic effects of the judicious nanostructure engineering of BiSbSx nanocrystals as well as the chemical interaction and confinement of SPAN fibers.

Exploring a more reasonable temperature exposure calculation method based on individual exposure survey and city-scale heat exposure impact assessment.

The inability to quantify the difference between ambient temperature (AT) and personal exposure temperature (PET) is a common limitation in environmental health research. The actual exposure variability is underestimated when we used measurements from fixed monitoring stations to estimate PET. The study aims to explore a more reasonable temperature exposure calculation method to relate PET to AT and links heat exposure to adverse health events. We measured hourly PET of 129 participants from July 8th to July 13th, 2021 in Xinyi City, China. The linear mixed-effects model was used to build the relationship between hourly PET and AT in rural and town. Several calculation methods that can capture the intensity, frequency and duration of daily exposure were used to calculate the daily PET and AT and establish the relationship between the two factors. A generalized linear model was used to establish the relationship between city-scale AT indicators and health endpoints from January 1st, 2013 to December 31st, 2015 in Shanghai, China. The result showed that the hourly PET was significantly related to AT, wind speed, air pressure, precipitation, outside time, and air-conditioning use. Among several daily temperature indicators, we found that ATDHAT (Degree Hours Above Threshold (27.4 °C)) was tight with the PETDHAT in different regions (R2 > 0.99). DHAT strengthened the relationship between daily AT and health endpoint in the urban-scale heat-related health impact study, especially in respiratory diseases. The method proposed in this study can improve the accuracy of future epidemiological studies on the effects of heat exposure.

Spatial heterogeneity in health risks of illness-related absenteeism associated with PM2.5 exposure for elementary students.

Little is known about the impact of socio-economic and environmental factors on the associations between PM2.5 exposure and health risk for elementary students. We estimated the space variability of effects of PM2.5 on daily illness-related absence rate for 2278 elementary schools from 97 counties across Jiangsu Province with data collected in the 2016-17 academic year. We evaluated the effects at school- and county-scales and examined the role of socio-economic and environmental factors with generalized addictive models (GAM). With an interquartile range (IQR, 32 µg/m3) increase in PM2.5 concentration, the relative risk of absence rate for a given school ranged between 1.00 and 2.81. Factors including high economic development level, low health expenditure, dense road network, dense population and low vegetation coverage drove strong effects for schools/counties. For the implementation of efficient clean air policies and public health interventions, we should concern about not only high-polluted areas but also areas under specific socio-economic and environmental conditions.

Harmine targets inhibitor of DNA binding-2 and activator protein-1 to promote preosteoclast PDGF-BB production.

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet-derived growth factor-BB (PDGF-BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF-BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding-2 (Id2) and activator protein-1 (AP-1) were important factors implicated in harmine-enhanced preosteoclast PDGF-BB production. Exposure of RANKL-induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP-1. Knockdown of Id2 by Id2-siRNA reduced the number of preosteoclasts as well as secretion of PDGF-BB in RANKL-stimulated BMMs administrated with harmine. Inhibition of c-Fos or c-Jun (components of AP-1) both reversed the stimulatory effect of harmine on preosteoclast PDGF-BB production. Dual-luciferase reporter assay analyses determined that PDGF-BB was the direct target of AP-1 which was up-regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF-BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.

Upregulated microRNA let-7a accelerates apoptosis and inhibits proliferation in uterine junctional zone smooth muscle cells in adenomyosis under conditions of a normal activated hippo-YAP1 axis.

BACKGROUND: Let-7a is a small non-coding RNA that has been found to take part in cell proliferation and apoptosis. The hippo-YAP1 axis, known as a tumour suppressor pathway, also plays an important role in cell proliferation and apoptosis. YAP1, TAZ, and phospho-YAP1 play key roles in actions of the hippo-YAP1 axis. Adenomyosis (ADS) is a proliferative disease leading to a large uterus in patients with prolonged illness. Abnormal proliferation of smooth muscle cells (SMCs) in the uterine endometrial-myometrial junctional zone (JZ) is an important reason for developing ADS. This study aimed to explore the expression levels of let-7a and components of the hippo-YAP1 axis in SMCs in the uterine endometrial-myometrial JZ in ADS and to explore the roles of let-7a and the hippo-YAP1 axis of JZ SMC proliferation and apoptosis in ADS. METHODS: We collected JZ tissues for the primary culture of SMCs from 25 women diagnosed with ADS and 27 women without ADS. We used quantitative real-time polymerase chain reaction and western blotting to measure the mRNA and protein expression levels of let-7a, YAP1, TAZ, and phospho-YAP1 in ADS JZ SMCs. A CCK-8 assay and flow cytometry analysis of apoptosis were utilized to test the proliferation and apoptosis of JZ SMCs. The let-7a overexpression lentiviral vector GV280 was used to increase the expression level of let-7a. We added verteporfin to block the phosphorylation of components of the hippo-YAP1 axis. RESULTS: We found that the let-7a level was decreased, while the YAP1 and TAZ levels were increased in ADS JZ SMCs. Upregulated let-7a affected the expression levels of components of the hippo-YAP1 axis, accelerated apoptosis, and inhibited proliferation in JZ SMCs. Furthermore, accumulated YAP1 led to increasing proliferation of JZ SMCs after verteporfin treatment to block the phosphorylation of components of the hippo-YAP1 axis. If components of the hippo-YAP1 axis were unphosphorylated, upregulated let-7a could not inhibit the proliferation of ADS JZ SMCs. Upregulated let-7a could not activate the hippo-YAP1 axis in verteporfin treatment. CONCLUSIONS: Our findings suggest that the let-7a and hippo-YAP1 axis may act as important regulators of JZ SMCs proliferation, and upregulated let-7a may be an effective method to treat ADS.