Galectin-3 contributes to pathogenesis of IgA nephropathy.

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis, and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.

The role of galectins in the regulation of autophagy and inflammasome in host immunity.

Galectins, a family of glycan-binding proteins have been shown to bind a wide range of glycans. In the cytoplasm, these glycans can be endogenous (or "self"), originating from damaged endocytic vesicles, or exogenous (or "non-self"), found on the surface of invading microbial pathogens. Galectins can detect these unusual cytosolic exposures to glycans and serve as critical regulators in orchestrating immune responses in innate and adaptive immunity. This review provides an overview of how galectins modulate host cellular responses, such as autophagy, xenophagy, and inflammasome-dependent cell death program, to infection.

The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Galectin-3 aggravates microglial activation and tau transmission in tauopathy.

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.

Age-specific percentile-based prostate-specific antigen cutoff values predict the risk of prostate cancer: A single hospital observation.

Background: Testing for prostate-specific antigen (PSA) is often recommended for men with a potential risk of prostate cancer (PCa) before requiring advanced examination. However, the best PSA cutoff value remains controversial. Object: We compared the predictive performance of age-specific percentile-based PSA thresholds with a conventional cutoff of >4 ng/mL for the risk of PCa. Methods: We included men who received PSA measurements between 2003 and 2017 in a medical center in Taiwan. Logistic regression modeling was used to assess the association between age-specific percentile-based PSA thresholds and PCa risk in age subgroups. We further applied C-statistic and decision curve analysis to compare the predictive performance of age-specific percentile-based PSA with that of a conventional cutoff PSA. Results: We identified 626 patients with PCa and 40 836 patients without PCa. The slope of PSA in patients >60-year-old was almost 3 times that of those <60-year-old (0.713 vs 0.259). The risk effect sizes of the 75th percentile PSA cutoff (<60-year-old: 2.19; 60-70-year-old: 4.36; >70-year-old: 5.84 ng/mL) were comparable to those observed based on the conventional cutoff in all age groups. However, the discrimination performance of the 75th percentile PSA cutoff was better than that of the conventional cutoff among patients aged <60-year-old (C-statistic, 0.783 vs. 0.729, p < 0.05). The 75th percentile cutoffs also correctly identified an additional 2 patients with PCa for every 100 patients with PSA screening at the threshold probability of 20%. Conclusions: Our data support the use of the 75th percentile PSA cutoff to facilitate individualized risk assessment, particularly for patients aged <60-year-old.

Galectin-12 Regulates Immune Responses in the Skin through Sebaceous Glands.

Sebaceous glands (SGs) are holocrine glands that produce sebum, which primarily contains lipids that help to maintain the barrier function of the skin. Dysregulated lipid production contributes to the progression of some diseases characterized by dry skin, including atopic dermatitis. Although the lipid production of SGs has been well-studied, few studies have assessed their role in skin immune responses. We found that SGs and sebocytes expressed IL-4 receptor and produced high levels of T helper 2-associated inflammatory mediators after IL-4 treatment, suggesting immunomodulatory effects. Galectin-12 is a lipogenic factor expressed in sebocytes that affects their differentiation and proliferation. Using galectin-12-knockdown sebocytes, we showed that galectin-12 regulated the immune response in cells exposed to IL-4 and promoted CCL26 expression by upregulating peroxisome proliferator-activated receptor-γ. Moreover, galectin-12 suppressed the expression of endoplasmic reticulum stress-response molecules, and CCL26 upregulation by IL-4 was reversed after sebocyte treatment with inducers of endoplasmic reticulum stress, suggesting that galectin-12 controls IL-4 signaling by suppressing endoplasmic reticulum stress. Using galectin-12-knockout mice, we showed that galectin-12 positively regulated the IL-4-induced enlargement of SGs and the development of an atopic dermatitis-like phenotype. Thus, galectin-12 regulates the skin immune response by promoting peroxisome proliferator-activated receptor-γ expression and suppressing endoplasmic reticulum stress in SGs.

Sialylation of cell surface glycoconjugates modulates cytosolic galectin-mediated responses upon organelle damage : Minireview.

Sialylation is an important terminal modification of glycoconjugates that mediate diverse functions in physiology and disease. In this review we focus on how altered cell surface sialylation status is sensed by cytosolic galectins when the integrity of intracellular vesicles or organelles is compromised to expose luminal glycans to the cytosolic milieu, and how this impacts galectin-mediated cellular responses. In addition, we discuss the roles of mammalian sialidases on the cell surface, in the organelle lumen and cytosol, and raise the possibility that intracellular glycan processing may be critical in controlling various galectin-mediated responses when cells encounter stress.

Dietary Supplementation with Milk Lipids Leads to Suppression of Developmental and Behavioral Phenotypes of Hyperexcitable Drosophila Mutants.

Dietary modifications often have a profound impact on the penetrance and expressivity of neurological phenotypes that are caused by genetic defects. Our previous studies in Drosophila melanogaster revealed that seizure-like phenotypes of gain-of-function voltage-gated sodium (Nav) channel mutants (paraShu, parabss1, and paraGEFS+), as well as other seizure-prone "bang-sensitive" mutants (eas and sda), were drastically suppressed by supplementation of a standard diet with milk whey. In the current study we sought to determine which components of milk whey are responsible for the diet-dependent suppression of their hyperexcitable phenotypes. Our systematic analysis reveals that supplementing the diet with a modest amount of milk lipids (0.26% w/v) mimics the effects of milk whey. We further found that a minor milk lipid component, α-linolenic acid, contributed to the diet-dependent suppression of adult paraShu phenotypes. Given that lipid supplementation during the larval stages effectively suppressed adult paraShu phenotypes, dietary lipids likely modify neural development to compensate for the defects caused by the mutations. Consistent with this notion, lipid feeding fully rescued abnormal dendrite development of class IV sensory neurons in paraShu larvae. Overall, our findings demonstrate that milk lipids are sufficient to ameliorate hyperexcitable phenotypes in Drosophila mutants, providing a foundation for future investigation of the molecular and cellular mechanisms by which dietary lipids modify genetically induced abnormalities in neural development, physiology, and behavior.

Association between coronary artery calcium and all-cause mortality: A large single-center retrospective cohort study.

OBJECTIVE: Previous studies have revealed that coronary artery calcium is related to cardiovascular diseases and mortality. However, most studies have been conducted in Western countries and have excluded patients with pre-existing heart disease. We investigated the association between coronary artery calcium (CAC) and all-cause mortality in an Asian cohort and in subgroups stratified by age, sex, smoking, obesity, diabetes, cardiovascular disease, blood pressure, and biochemical parameters. METHODS: We conducted a retrospective cohort study on 4529 health examinees who underwent multidetector computed tomography in a tertiary medical center in Taiwan between 2011 and 2016. The mean follow-up was 3.5 years. Cox regression was used to estimate the relative hazards of death. Stratified analyses were performed. RESULTS: The all-cause mortality rates were 2.94, 4.88, 17.6, and 33.1 per 1000 person-years for CAC scores of 0, 1-100, 101-400, and >400, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CIs]) for all-cause mortality were 0.95 (0.53, 1.72), 1.87 (0.89, 3.90), and 3.05 (1.46, 6.39) for CAC scores of 1-100, 101-400, and >400, respectively, relative to a CAC score of 0. Compared with CAC ≤ 400, the HRs (95% CIs) for CAC > 400 were 6.46 (2.44, 17.15) and 1.94 (1.00, 3.76) in younger and older adults, respectively, indicating that age was a moderating variable (p = 0.02). CONCLUSION: High CAC scores were associated with increased all-cause mortality. Although older adult patients had higher risks of death, the relative risk of death for patients with CAC > 400 was more prominent in people younger than 65 years.

Doping Mechanism of Perovskite Films with PbCl2 Prepared by Magnetron Sputtering for Enhanced Efficiency of Solar Cells.

The last decade has witnessed a rapid growth of perovskite solar cells extended from mesoporous to planar architecture as well as from solution processing to solvent-free fabrication. The preparation of perovskite films by solvent-free method still presents significant challenges, such as the difficulty of film preparation by multiple evaporation sources in vapor deposition and the immaturity of the sputtered method. Here, we present a planar perovskite solar cell fabricated by solvent-free magnetron sputtering without the assistance of the mesoporous TiO2 layer, and lead chloride (PbCl2) was mechanically milled into the target of methylammonium lead halides (MAPbI3) to improve the quality of perovskite film by regulating the crystallization process with the Cl element. Furthermore, the internal reason for the effect of different PbCl2 doping contents on the trap density of perovskite films was also investigated in detail. These lead to an improved power conversion efficiency of planar heterojunction perovskite solar cells up to 17.10%, which is the highest efficiency recorded for the sputtered perovskite solar cells so far. The stability of resulting solar cells has also been significantly improved by exploring the doping mechanism of perovskite films with PbCl2 in detail, showing great research and application prospect.

Association of water intake and hydration status with risk of kidney stone formation based on NHANES 2009-2012 cycles.

OBJECTIVE: Evaluating the association of water intake and hydration status with nephrolithiasis risk at the population level. DESIGN: It is a cross-sectional study in which daily total plain water intake and total fluid intake were estimated together with blood osmolality, urine creatinine, urine osmolality, urine flow rate (UFR), free water clearance (FWC) and urine/blood osmolality ratio (Uosm:Bosm). The associations of fluid intake and hydration markers with nephrolithiasis were evaluated using multivariable logistic regression. SETTING: General US population. PARTICIPANTS: A total of 8195 adults aged 20 years or older from the National Health and Nutritional Examination Survey 2009-2012 cycles. RESULTS: The population medians (interquartile ranges, IQR) for daily total plain water intake and total fluid intake were 807 (336-1481) and 2761 (2107-3577) ml/d, respectively. The adjusted OR (95 % CI) of nephrolithiasis for each IQR increase in total plain water intake and total fluid intake were 0·92 (95 % CI 0·79, 1·06) and 0·84 (95 % CI 0·72, 0·97), respectively. The corresponding OR of nephrolithiasis for UFR, blood osmolality, Uosm:Bosm and urine creatinine were 0·87 (95 % CI 0·76, 0·99), 1·18 (95 % CI 1·06, 1·32), 1·38 (95 % CI 1·17, 1·63) and 1·27 (95 % CI 1·11, 1·45), respectively. A linear protective relationship of fluid intake, UFR and FWC with nephrolithiasis risk was observed. Similarly, positive dose-response associations of nephrolithiasis risk with markers of insufficient hydration were identified. Encouraging a daily water intake of >2500 ml/d and maintaining a urine output of 2 l/d was associated with a lower prevalence of nephrolithiasis. CONCLUSION: This study verified the beneficial role of general water intake recommendations in nephrolithiasis prevention in the general US population.

Photoreduction of carbon dioxide and photodegradation of organic pollutants using alkali cobalt oxides MCoO2 (M = Li or Na) as catalysts.

The recycling of lithium batteries should be prioritized, and the use of discarded alkali metal battery electrode materials as photocatalysts merits research attention. This study synthesized alkali metal cobalt oxide (MCoO2, M = Li or Na) as a photocatalyst for the photoreduction of CO2 and degradation of toxic organic substances. The optimized NaCoO2 and LiCoO2 photocatalysts increased the photocatalytic CO2-CH4 conversion rate to 21.0 and 13.4 µmol g-1 h-1 under ultraviolet light irradiation and to 16.2 and 5.3 µmol g-1 h-1 under visible light irradiation, which is 17 times higher than that achieved by TiO2 P25. The rate constants of the optimized reactions of crystal violet (CV) with LiCoO2 and NaCoO2 were 2.29 × 10-2 and 4.35 × 10-2 h-1, respectively. The quenching effect of the scavengers and electron paramagnetic resonance in CV degradation indicated that active O2•-, 1O2, and h+ play the main role, whereas •OH plays a minor role for LiCoO2. The hyperfine splitting of the DMPO-•OH and DMPO-•CH3 adducts was aN = 1.508 mT, aHß = 1.478 mT and aN = 1.558 mT, aHß = 2.267 mT, respectively, whereas the hyperfine splitting of DMPO+• was aN = 1.475 mT. The quenching effect also indicated that active O2•- and h+ play the main role and that •OH and 1O2 play a minor role for NaCoO2. The hyperfine splitting of the DMPO-•OH and DMPO+• adducts was aN = 1.517 mT, aHß = 1.489 mT and aN = 1.496 mT, respectively. Discarded alkali metal battery electrode materials can be reused as photocatalysts to address environmental pollution.

Organic-Inorganic Perovskite Films and Efficient Planar Heterojunction Solar Cells by Magnetron Sputtering.

Organic-inorganic halide perovskites have been widely used in photovoltaic technologies. Despite tremendous progress in their efficiency and stability, perovskite solar cells (PSCs) are still facing the challenges of upscaling and stability for practical applications. As a mature film preparation technology, magnetron sputtering has been widely used to prepare metals, metallic oxides, and some semiconductor films, which has great application potential in the fabrication of PSCs. Here, a unique technology where high-quality perovskite films are prepared via magnetron sputtering for controllable composition, solvent-free, large-area, and massive production, is presented. This strategy transforms the perovskite materials from powder to thin films by magnetron sputtering and post-treatment (vapor-assisted treatment with methanaminium iodide gas and methylamine gas treatment), which is greatly favorable to manufacture tandem solar cells. The power conversion efficiency (PCE) of PSCs with perovskite films fabricated by magnetron sputtering is 6.14%. After optimization, high-performance perovskite films with excellent electronic properties are obtained and stable PSCs with excellent reproducibility are realized, showing a PCE of up to 15.22%. The entirely novel synthetic approach opens up a new and promising way to achieve high-throughput magnetron sputtering for large-area production in commercial applications of planar heterojunction and tandem PSCs.

Galectin-3 promotes noncanonical inflammasome activation through intracellular binding to lipopolysaccharide glycans.

Cytosolic lipopolysaccharides (LPSs) bind directly to caspase-4/5/11 through their lipid A moiety, inducing inflammatory caspase oligomerization and activation, which is identified as the noncanonical inflammasome pathway. Galectins, ß-galactoside-binding proteins, bind to various gram-negative bacterial LPS, which display ß-galactoside-containing polysaccharide chains. Galectins are mainly present intracellularly, but their interactions with cytosolic microbial glycans have not been investigated. We report that in cell-free systems, galectin-3 augments the LPS-induced assembly of caspase-4/11 oligomers, leading to increased caspase-4/11 activation. Its carboxyl-terminal carbohydrate-recognition domain is essential for this effect, and its N-terminal domain, which contributes to the self-association property of the protein, is also critical, suggesting that this promoting effect is dependent on the functional multivalency of galectin-3. Moreover, galectin-3 enhances intracellular LPS-induced caspase-4/11 oligomerization and activation, as well as gasdermin D cleavage in human embryonic kidney (HEK) 293T cells, and it additionally promotes interleukin-1ß production and pyroptotic death in macrophages. Galectin-3 also promotes caspase-11 activation and gasdermin D cleavage in macrophages treated with outer membrane vesicles, which are known to be taken up by cells and release LPSs into the cytosol. Coimmunoprecipitation confirmed that galectin-3 associates with caspase-11 after intracellular delivery of LPSs. Immunofluorescence staining revealed colocalization of LPSs, galectin-3, and caspase-11 independent of host N-glycans. Thus, we conclude that galectin-3 amplifies caspase-4/11 oligomerization and activation through LPS glycan binding, resulting in more intense pyroptosis-a critical mechanism of host resistance against bacterial infection that may provide opportunities for new therapeutic interventions.

Visible-light-driven photocatalysis of carbon dioxide and organic pollutants by MFeO2 (M = Li, Na, or K).

In recent years, lithium-containing ceramic materials have attracted considerable research attention as high-temperature adsorbents of carbon dioxide. The recycling of electrode materials from spent lithium-ion batteries for use as photocatalysts in recovering CO2 and degrading organic pollutants is worthy of exploration. Solid, magnetic ferrite-containing photocatalysts are easily separated from reaction solutions by using magnetic devices. Solid catalysts (e.g., LiFeO2, LiFe5O8, NaFeO2, and K2Fe2O4) were prepared through the calcination of Fe2O3 and M2CO3. CO2 was photoreduced and crystal violet (CV) and 2-hydroxybenzoic acid (2-HBA) were photodegraded under visible light irradiation. The optimized K2Fe2O4 photocatalyst increased the rate of photocatalytic conversion from CO2 to methane at 20.9 µmol g-1 h-1. The catalytic efficiency indicated that the optimized reaction rate constants of CV with LiFeO2, NaFeO2, and K2Fe2O4 were 2.98 × 10-1, 5.32 × 10-1, and 4.36 × 10-1 h-1, respectively. The quenching effect achieved through the use of various scavengers and the electron paramagnetic resonance in CV degradation revealed the substantial contribution of the reactive superoxide anion radical O2- and the minor roles of h+ and the OH radical. Its usefulness in the synthesis of solid-base catalyst MFeO2 is promising for environmental control and relevant applications, particularly in solar energy manufacturing.

Effects of acute heat stress on protein expression and histone modification in the adrenal gland of male layer-type country chickens.

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 roosters were subject to acute heat stress and thereafter classified into a resistant or susceptible group according to body temperature change. The iTRAQ analysis identified 80 differentially expressed proteins, in which the resistant group had a higher level of somatostatin and hydroxy-δ-5-steroid dehydrogenase but a lower parathymosin expression in accordance with the change of serum glucocorticoid levels. Histone modification analysis identified 115 histone markers. The susceptible group had a higher level of tri-methylation of histone H3 lysine 27 (H3K27me3) and showed a positive crosstalk with K36me and K37me in the H3 tails. The differential changes of body temperature projected in physiological regulation at the hypothalamus-pituitary-adrenal axis suggest the genetic heterogeneity in basic metabolic rate and efficiency for heat dissipation to acclimate to thermal stress and maintain body temperature homeostasis. The alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal gland and may contribute to the thermotolerance of chickens.

Targeted disruption of galectin 3 in mice delays the first wave of spermatogenesis and increases germ cell apoptosis.

Galectin 3 is a multifunctional lectin implicated in cellular proliferation, differentiation, adhesion, and apoptosis. This lectin is broadly expressed in testicular somatic cells and germ cells, and is upregulated during testicular development. Since the role of galectin 3 in testicular function remains elusive, we aimed to characterize the role of galectin 3 in testicular physiology. We found that galectin 3 transgenic mice (Lgals3-/-) exhibited significantly decreased testicular weight in adulthood compared to controls. The transgenic mice also exhibited a delay to the first wave of spermatogenesis, a decrease in the number of germ cells at postnatal day 5 (P5) and P15, and defective Sertoli cell maturation. Mechanistically, we found that Insulin-like-3 (a Leydig cell marker) and enzymes involved in steroid biosynthesis were significantly upregulated in adult Lgals3-/- testes. These observations were accompanied by increased serum testosterone levels. To determine the underlying causes of the testicular atrophy, we monitored cellular apoptosis. Indeed, adult Lgals3-/- testicular cells exhibited an elevated apoptosis rate that is likely driven by downregulated Bcl-2 and upregulated Bax and Bak expression, molecules responsible for live/death cell balance. Moreover, the percentage of testicular macrophages within CD45+ cells was decreased in Lgals3-/- mice. These data suggest that galectin 3 regulates spermatogenesis initiation and Sertoli cell maturation in part, by preventing germ cells from undergoing apoptosis and regulating testosterone biosynthesis. Going forward, understanding the role of galectin 3 in testicular physiology will add important insights into the factors governing the development of germ cells and steroidogenesis and delineate novel biomarkers of testicular function.

Mechanochemical synthesis of pure phase mixed-cation/anion (FAPbI3) x (MAPbBr3)1-x hybrid perovskite materials: compositional engineering and photovoltaic performance.

Organic-inorganic hybrid perovskites have emerged as promising light harvesting materials for many optoelectronic devices. Here, we present a facile mechanochemical synthesis (MCS) route for the preparation of a series of pure phase mixed-cation/anion (FAPbI3) x (MAPbBr3)1-x (0 ≤ x ≤ 1) hybrid perovskite materials for high-efficiency thin-film perovskite solar cells (PSCs). The use of (α-FAPbI3)0.95(MAPbBr3)0.05 perovskite prepared by MCS for the thin-film PSCs achieves a maximum PCE of 15.9% from a current-voltage (J-V) scan, which stabilises at 15.4% after 120 s of the maximum power point output. Furthermore, PSCs based on (KPbI3)0.05(FAPbI3)0.9(MAPbBr3)0.05 perovskite prepared by MCS exhibit higher photovoltaic performance and lower hysteresis compared with (α-FAPbI3)0.95(MAPbBr3)0.05, with a maximum PCE of 16.7%. These results indicate that the use of mechanochemically synthesised perovskites provides a promising strategy for high performance PSCs and superior control in optoelectronic properties, leading to improved control in fabrication approaches and facilitating the development of efficient and stable PSCs in the future.

Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.

Galectin-8 Is Upregulated in Keratinocytes by IL-17A and Promotes Proliferation by Regulating Mitosis in Psoriasis.

Psoriasis is a chronic inflammatory skin disease that develops under the influence of the IL-23/T helper 17 cell axis and is characterized by intense inflammation and prominent epidermal hyperplasia. In this study, we demonstrate that galectin-8, a ß-galactoside‒binding lectin, is upregulated in the epidermis of human psoriatic skin lesions as well as in a mouse model of psoriasis induced by intradermal IL-23 injections and in IL-17A‒treated keratinocytes. We show that keratinocyte proliferation is less prominent in galectin-8‒knockout mice after intradermal IL-23 treatment than in wild-type mice. In addition, we show that galectin-8 levels in keratinocytes are positively correlated with the ability of the cells to proliferate and that transitioning from mitosis into G1 phase is delayed in galectin-8‒knockout HaCaT cells after cell-cycle synchronization and release. We demonstrate by immunofluorescence staining and immunoblotting the presence of galectin-8 within the mitotic apparatus. We reveal by coimmunoprecipitation and mass spectrometry analysis that α-tubulin interacts with galectin-8 during mitosis. Finally, we show that in the absence of galectin-8, pericentrin compactness is lessened and mitotic microtubule length is shortened, as demonstrated by immunofluorescence staining. We conclude that galectin-8 is upregulated in psoriasis and contributes to the hyperproliferation of keratinocytes by maintaining centrosome integrity during mitosis through interacting with α-tubulin.