SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer worldwide. Structural maintenance of chromosomes 2 (SMC2) serves as a predictor of poor prognosis across various cancer types. This study aims to explore the role and underlying mechanisms of SMC2 in LUAD progression. The expression of SMC2 in LUAD tissues and its correlation with prognosis were analyzed by public databases. Knockdown of SMC2 was performed to assess the proliferation, migration and invasion ability of LUAD cells. Bulk RNA sequencing analysis identified enriched cellular pathways and remarkable upregulation of BTG anti-proliferation factor 2 (BTG2) expression after SMC2 knockdown in LUAD cells. Then, BTG2 was silenced to assess the malignant behavior of LUAD cells. Subcutaneous transplantation and intracranial tumor models of LUAD cells in BALB/c nude mice were established to assess the antineoplastic effect of SMC2 knockdown in vivo. Additionally, a lung metastasis model was created to evaluate the pro-metastatic effect of SMC2. Our findings indicated that SMC2 was upregulated in LUAD tissues and cell lines, with higher expression correlating with poor prognosis. SMC2 silencing suppressed the proliferation, migration and invasion ability of LUAD cells by upregulating BTG2 expression via p53 and inactivating ERK and AKT pathways. BTG2 silencing reversed the effects of SMC2 downregulation on malignant behaviors of LUAD cells and restored the phosphorylated ERK and AKT levels. Furthermore, SMC2 knockdown effectively prevented the formation of subcutaneous, intracranial and metastatic tumor in vivo, and upregulation of BTG2 expression after SMC2 knockdown was confirmed in tumor models. This study revealed that SMC2 knockdown restrained the malignant progression of LUAD through upregulation of BTG2 expression and inactivation of ERK and AKT pathways, and SMC2 could be a potential therapeutic target for LUAD treatment.

In Situ Polymerized Self-Healing Microcapsules as Multifunctional Fillers toward Phosphate Ceramic Coatings.

The protective efficacy of chemically bonded phosphate ceramic coatings (CBPC) is notably diminished owing to the presence of micropores and inadequate self-healing capacity in prolonged corrosive environments. Consequently, it is imperative to augment the corrosion and wear resistance of phosphate ceramic coatings while imbuing them with self-healing capabilities. In this work, a novel self-healing phosphate ceramic coating (MC-PTx@CBPC, x = 0.5, 1.0, 1.5) is designed by urea-formaldehyde (UF) in situ polymerization of nanoscale microcapsules encapsulated with 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES) and evaluated in detail for corrosion and wear resistance. The corrosion inhibition efficiencies of all formulated MC-PTx@CBPC (x = 0.5, 1.0, 1.5) coatings exceed 90%, with the impedance modulus at the lowest frequency (|Z|f=0.01) showing enhancements of 1-2 orders of magnitude compared to pure CBPC. Moreover, the self-healing function becomes active during prolonged immersion. This can be primarily ascribed to the formation of a unique micronanostructure facilitated by nanoscale microcapsules and micrometer-sized alumina ceramics, bonded via the AlPO4 phase. This structure enhances both the hydrophobicity and the bonding strength of the coating. Specifically, following prolonged immersion, the encapsulated PFDTES is liberated from the microcapsules, undergoing hydrolysis and subsequent polymerization upon contact with the electrolyte to form a protective thin film. This film efficiently obstructs the ingress of corrosive agents. Furthermore, the special micronanostructure enhances the hardness of the coating and the releasing PFDTES can form a lubricating film at the interface of abrasion, thus reducing the wear rate and friction coefficient of the MC-PTx@CBPC (x = 0.5, 1.0, 1.5). Therefore, MC-PTx@CBPC (x = 0.5, 1.0, 1.5) possesses excellent corrosion protection, tribological properties, and self-healing capabilities, which provide thought-provoking ideas for phosphate ceramic coatings to protect metals in harsh environments.

Trimethyl chitosan-cysteine-based nanoparticles as an effective delivery system for portulacerebroside A in the management of hepatocellular carcinoma cells in vitro and in vivo.

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.

Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Gut microbiome-metabolites axis: A friend or foe to colorectal cancer progression.

An expanding corpus of research robustly substantiates the complex interrelation between gut microbiota and the onset, progression, and metastasis of colorectal cancer. Investigations in both animal models and human subjects have consistently underscored the role of gut bacteria in a variety of metabolic activities, driven by dietary intake. These activities include amino acid metabolism, carbohydrate fermentation, and the generation and regulation of bile acids. These metabolic derivatives, in turn, have been identified as significant contributors to the progression of colorectal cancer. This thorough review meticulously explores the dynamic interaction between gut bacteria and metabolites derived from the breakdown of amino acids, fatty acid metabolism, and bile acid synthesis. Notably, bile acids have been recognized for their potential carcinogenic properties, which may expedite tumor development. Extensive research has revealed a reciprocal influence of gut microbiota on the intricate spectrum of colorectal cancer pathologies. Furthermore, strategies to modulate gut microbiota, such as dietary modifications or probiotic supplementation, may offer promising avenues for both the prevention and adjunctive treatment of colorectal cancer. Nevertheless, additional research is imperative to corroborate these findings and enhance our comprehension of the underlying mechanisms in colorectal cancer development.

Explaining demographic-destination preferences for cultural ecosystem services: A set-theoretic configurational analysis.

Many fundamental studies on cultural ecosystem services (CES) and CES destination preferences still tend to focus on detecting the respective importance of destination attributes. However, this perspective needs more efforts on the fact that visitors always select a CES destination through a configurational consideration of its ecological and environmental attributes. Based on this consideration, 22 urban green spaces in Nagoya, Japan were studied, and a configurational model was developed by applying complexity theory and qualitative comparative analysis (QCA), to explain and better understand the causal patterns of CES quality and availability influencing demographic-CES destination preferences. The results showed that similar preference modes occurred between young adults and males who were very concerned about the time spent on transportation, and between older people and females who had multiple considerations regarding both CES quality and availability. Such findings on the demographic-destination preferences for CES could not only provide configurational insight into the relationships between destination attributes and travel preferences, but also help CES organizations develop multi-factor cooperative management for better CES provision.

The Association Between Dietary Magnesium Intake with Chronic Obstructive Pulmonary Disease and Lung Function in US Population: a Cross-sectional Study.

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [ß = 0.21 (95% CI 0.12, 0.30)] and FVC [ß = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.

Differentiable Design Galleries: A Differentiable Approach to Explore the Design Space of Transfer Functions.

The transfer function is crucial for direct volume rendering (DVR) to create an informative visual representation of volumetric data. However, manually adjusting the transfer function to achieve the desired DVR result can be time-consuming and unintuitive. In this paper, we propose Differentiable Design Galleries, an image-based transfer function design approach to help users explore the design space of transfer functions by taking advantage of the recent advances in deep learning and differentiable rendering. Specifically, we leverage neural rendering to learn a latent design space, which is a continuous manifold representing various types of implicit transfer functions. We further provide a set of interactive tools to support intuitive query, navigation, and modification to obtain the target design, which is represented as a neural-rendered design exemplar. The explicit transfer function can be reconstructed from the target design with a differentiable direct volume renderer. Experimental results on real volumetric data demonstrate the effectiveness of our method.

Biomimetic Corneal Stroma for Scarless Corneal Wound Healing via Structural Restoration and Microenvironment Modulation.

Corneal injury-induced stromal scarring causes the most common subtype of corneal blindness, and there is an unmet need to promote scarless corneal wound healing. Herein, a biomimetic corneal stroma with immunomodulatory properties is bioengineered for scarless corneal defect repair. First, a fully defined serum-free system is established to derive stromal keratocytes (hAESC-SKs) from a current Good Manufacturing Practice (cGMP)-grade human amniotic epithelial stem cells (hAESCs), and RNA-seq is used to validate the phenotypic transition. Moreover, hAESC-SKs are shown to possess robust immunomodulatory properties in addition to the keratocyte phenotype. Inspired by the corneal stromal extracellular matrix (ECM), a photocurable gelatin-based hydrogel is fabricated to serve as a scaffold for hAESC-SKs for bioengineering of a biomimetic corneal stroma. The rabbit corneal defect model is used to confirm that this biomimetic corneal stroma rapidly restores the corneal structure, and effectively reshapes the tissue microenvironment via proteoglycan secretion to promote transparency and inhibition of the inflammatory cascade to alleviate fibrosis, which synergistically reduces scar formation by ≈75% in addition to promoting wound healing. Overall, the strategy proposed here provides a promising solution for scarless corneal defect repair.

Tumor acidity-activatable macromolecule autophagy inhibitor and immune checkpoint blockade for robust treatment of prostate cancer.

Immune checkpoint blockade (ICB) antibody such as anti-PD-L1 (aPD-L1) activates cytotoxic T cells (CTLs) to combat cancer, but they showed poor efficacy in prostate cancer (PCa). Lysosome-dependent autophagy is utilized by cancer cells to degrade their MHC-I and to lower their vulnerability to TNF-α and CTLs. Lysosomal pH-sensitive polymeric nanoparticle as a drug delivery carrier may also be a novel autophagy inhibitor to boost immunotherapy, but such an important effect has not been investigated. Herein, we developed a unique tumor acidity-activatable macromolecular nanodrug (called P-PDL1-CP) with the poly(2-diisopropylaminoethyl methacrylate) (PDPA) core and the conjugations of both aPD-L1 and long-chain polyethylene glycol (PEG) coating. The PDPA core was demonstrated to disturb lysosome to block the autophagic flux, thus elevating the cancer cell's MHC-I expression and vulnerability to the TNF-α and CTLs. Long-chain PEG facilitated a good tumor accumulation of P-PDL1-CP nanodrug. Furthermore, P-PDL1-CP nanodrug inhibited tumor autophagy, which synergized with aPD-L1 to promote the tumor-infiltrating CTLs and DCs maturation, to elevate intratumoral TNF-α and IFN-γ levels, and to elicit an anti-tumor immune memory effect in mice for PCa growth inhibition with low side effects. This study verified the synergistic anti-PCa treatment between autophagy inhibition and PD-L1 blockade and meantime broadened the application of pH-sensitive macromolecular nanodrug. STATEMENT OF SIGNIFICANCE: A macromolecular nanodrug, comprising the PDPA core and the surface conjugation of both aPD-L1 antibodies and long-chain PEG coating via a tumor acidity-labile α-carboxy-dimethylmaleic anhydride amine bond, was developed. Tumoral acidity triggered the release of aPD-L1 for immunotherapy. Meantime, the charge switch of the remanent nanodrug enhanced the cancer cell uptake of PDPA, which disturbed the lysosomes to inhibit autophagy. This advanced nanodrug promoted the tumor-infiltrating CTLs and DCs maturation, elevated the intratumoral TNF-α and IFN-γ levels, and elicited the robust anti-tumor immune memory effect. This study demonstrated that the pH-sensitive PDPA macromolecule could serve as a carrier for the aPD-L1 delivery and as an efficient autophagy inhibitor to boost the immunotherapy of prostate cancer.

Retinol-binding protein-hijacking nanopolyplex delivering siRNA to cytoplasm of hepatic stellate cell for liver fibrosis alleviation.

Activated hepatic stellate cell (aHSC) is mainly responsible for deposition of extracellular collagen matrix that causes liver fibrosis. Although several siRNAs adequately inhibited HSC activation in vitro, they were demonstrated poor RNAi efficiency in vivo. Developing HSC-targeting and cytoplasmic delivery nanocarrier is highly essential to acquire a desirable siRNA therapeutic index for anti-liver fibrosis. Here, we developed a unique crosslinking nanopolyplex (called T-C-siRNA) modified by vitamin A (VA) with the well-designed natures, including the negative charge, retinol-binding protein (RBP) hijacking, and cytoplasmic siRNA release in response to ROS and cis diol molecules. The nanopolyplex was given a yolk-shell-like shape, camouflage ability in blood, and HSC-targeting capability by hijacking the endogenous ligand RBP via surface VA. PDGFR-ß siRNA (siPDGFR-ß) supplied via T-C-siPDGFR-ß nanopolyplex dramatically reduced HSC activation and its production of pro-fibrogenic proteins in vitro and in vivo. Furthermore, T-C-siPDGFR-ß nanopolyplex effectively alleviated CCl4-induced liver injury, decreased hepatic collagen sediment, and recovered liver function in mice. This study provides a sophisticated method for HSC-targeting cytoplasmic RNA delivery using endogenous ligand hijacking and dual sensitivity of ROS and cis diol compounds.

Using intermittent moving aeration to repair hypereutrophic pond: nutrient removal efficiency and microbial diversity analysis.

This study presents a novel perspective on the control of eutrophication by moving aeration through a ten-month pilot field study. Moving aeration significantly reduced the relative abundance of class Cyanobacteria by 14.01%, effectively preventing cyanobacteria from predominating in the overlying water. As a result, the deposition of TOC, N, and P in the surface of the sediment decreased by 90%, 73%, and 93% in comparison to the control group. The analysis of microbial community structure based on 16S rRNA high-throughput sequencing showed that the order Bacillales and Micrococcales contributed to nitrogen removal significantly increased by 19.44% and 3.94%, respectively, while the order Steroidobacterales, Rhizobiales, and Microtrichales involved in the immobilization of carbon and nitrogen were significantly decreased by 4.03%, 2.69%, and 2.3% in the aeration group, respectively. Variation in the number of functional microorganisms based on the MPN method revealed that moving aeration promoted the growth of nitrifying bacteria and denitrifying bacteria. These findings demonstrated that moving aeration is effective in repairing eutrophic water and eliminating endogenous N pollutants.

Fine-Tuned Polymer Nanoassembly for Codelivery of Chemotherapeutic Drug and siRNA.

Successful clinical application of siRNA to liver-associated diseases reinvigorates the RNAi therapeutics and delivery vectors, especially for anticancer combination therapy. Fine tuning of copolymer-based assembly configuration is highly important for a desirable synergistic cancer cell-killing effect via the codelivery of chemotherapeutic drug and siRNA. Herein, an amphiphilic triblock copolymer methoxyl poly(ethylene glycol)-block-poly(L-lysine)-block-poly(2-(diisopropyl amino)ethyl methacrylate) (abbreviated as mPEG-PLys-PDPA or PLD) consisting of a hydrophilic diblock mPEG-PLys and a hydrophobic block PDPA is synthesized. Three distinct assemblies (i.e., nanosized micelle, nanosized polymersome, and microparticle) are acquired, along with the increase in PDPA block length. Furthermore, the as-obtained polymersome can efficiently codeliver doxorubicin hydrochloride (DOX) as a hydrophilic chemotherapeutic model and siRNA against ADP-ribosylation factor 6 (siArf6) as an siRNA model into cancer cell via lysosomal pH-triggered payload release. PC-3 prostate cell is synergistically killed by the DOX- and siArf6-coloading polymersome (namely PLD@DOX/siArf6). PLD@DOX/siArf6 may serve as a robust nanomedicine for anticancer therapy.

Effects of overwintering cyanobacteria on phosphorus and iron regeneration across the sediment-water interface: A pilot simulation experiment.

Cyanobacterial blooms are a major environmental problem in eutrophic reservoirs in China. Algal cells can migrate to the sediment surface in winter and maintain biological activity, which could further affect the cycling process of sediment phosphorus (P) and iron (Fe). In this study, a pilot simulation experiment was conducted to investigate the effect of overwintering cyanobacteria (Owc) on P and Fe regeneration across the sediment-water interface (SWI). Owc esterase activity ranged from 16.4 to 26.6 nmol (FDA)/(L·h), with a fluctuating increasing trend within the incubation time. Compared with the control (no Owc), Owc treatment increased the redox potential value (Eh) at the SWI but slightly decreased the pH during the first stage of this experiment (0-24 d); however, the Eh at the SWI under Owc treatment decreased to 50.9 % of that of the control on day 90. The Fe(II) could rapidly oxidized to Fe (oxyhydro)oxides and combine with phosphate in high Eh environments, and Owc inhibited P and Fe release at the SWI within 24 days; however, the continuous decrease in Eh resulted in the reduction of Fe(III). Thus, the Fe concentration measured via diffusive gradients in thin films in the Owc-treated interstitial water gradually increased to 1.92 times that of the control, promoting the release of Fe and P across the SWI. For 13 days after Owc addition, the amount of mobile P in the sediment was significantly higher than that in the control, and it gradually decreased from day 24 to 90, with the lowest being approximately 74.1 % of the amount in the control. The reactive Fe concentration in the sediment showed a similar variation trend. These results indicate that mobile P and reactive Fe in the sediment could be the main sources of regeneration across the SWI in the presence of Owc.

Host defense against the infection of Klebsiella pneumoniae: New strategy to kill the bacterium in the era of antibiotics?

Klebsiella pneumoniae (K. pneumoniae) is a typical gram-negative iatrogenic bacterium that often causes bacteremia, pneumonia and urinary tract infection particularly among those with low immunity. Although antibiotics is the cornerstone of anti-infections, the clinical efficacy of ß-lactamase and carbapenems drugs has been weakened due to the emergence of drug-resistant K. pneumoniae. Recent studies have demonstrated that host defense plays a critical role in killing K. pneumoniae. Here, we summarize our current understanding of host immunity mechanisms against K. pneumoniae, including mechanical barrier, innate immune cells, cellular immunity and humoral immunity, providing a theoretical basis and the new strategy for the clinical treatment of K. pneumoniae through improving host immunity.

A novel clinical dynamic stereopsis assessment based on autostereoscopic display system.

Background: Although it is recognized that dynamic stereopsis is vital in daily life, there is still room for improvement in assessment methods. A novel clinical dynamic stereopsis assessment method was created based on an autostereoscopic display system that did not require additional auxiliary glasses. This study evaluated the optical parameters and clinical performance of the autostereoscopic display system for clinical dynamic stereopsis assessment. Methods: The autostereoscopic dynamic stereopsis assessment device was based on a directional backlight technology. Experiment 1 was performed under the same environmental conditions to compare luminance, crosstalk, and spectrum between the autostereoscopic dynamic stereopsis assessment device and the conventional dynamic random-dot stereopsis measuring instrument. Experiment 2 was an observational, analytic, cross-sectional study involving 135 healthy participants, each of whom was asked to complete measurements on both the autostereoscopic and conventional devices in random order. Stereo acuity, operating time, acceptance, and visual fatigue scores were recorded for clinical evaluation. Results: The autostereoscopic device had brighter luminance (139 and 140 cd/m2 for 2 eyes, respectively), lower crosstalk (4.50% for both eyes), and higher color restoration degree than those of the conventional instrument. Clinically, the novel dynamic stereopsis assessment was as accurate as the traditional method [170" (0.00") and 170" (0.00") respectively; P=0.317], and with more efficiency (166±58.9 and 298±116 s, respectively; P<0.001), higher acceptance (3.36±0.93 and 2.02±0.59 points, respectively; P<0.001), lesser fatigue (0.27±0.46 and 0.73±0.66 points, respectively; P<0.001). The autostereoscopic dynamic stereopsis assessment device with brighter luminance, lower crosstalk, and higher color restoration degree was more effective than the traditional instrument at displaying dynamic clues for clinical dynamic stereopsis assessment. Furthermore, its high-quality image and user-friendly interface provided accurate assessment results in all 3 dynamic stereopsis assessment task conditions, with a higher level of acceptance and lesser visual fatigue, than the traditional assessment method. Conclusions: The autostereoscopic device has excellent functions in both optical parameters and clinical performance, and therefore has the potential to be applied and popularized in future assessments.

Effects of Perceptual Learning on Deprivation Amblyopia in Children with Limbal Dermoid: A Randomized Controlled Trial.

Limbal dermoid (LD) is a congenital ocular tumor that causes amblyopia and damages visual acuity (VA) and visual function. This study evaluated the therapeutic efficacy of perceptual learning (PL) toward improving contrast sensitivity function (CSF) and VA. A total of 25 children with LD and 25 normal children were compared in terms of CSF and VA. The LD group was further randomly allocated into two arms: nine underwent PL combined with patching and eight underwent patching only; eight patients quit the amblyopia treatment. The primary outcome was the area under log CSF (AULCSF), and the secondary outcome was the best corrected VA (BCVA). The CSF was obviously reduced in the LD group compared with that in the normal group. Moreover, the difference in the changes in the AULCSF between the PL and patching groups after 6 months of training was 0.59 (95% CI: 0.32, 0.86, p < 0.001), and the between-group difference in VA at 6 months was −0.30 (95% CI: −0.46, −0.14, p < 0.001). Children suffering from LD with amblyopia exhibited CSF deficits and VA loss simultaneously. PL could improve CSF and VA in the amblyopic eye better than patching.

Mogroside V Improves Follicular Development and Ovulation in Young-Adult PCOS Rats Induced by Letrozole and High-Fat Diet Through Promoting Glycolysis.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In this study, we induced a young-adult PCOS rat model by oral administration of letrozole combined with a high-fat diet and then treated with mogroside V (MV) to evaluate the protective effects of MV on endocrine and follicle development in young-adult PCOS rats. MV (600 mg/kg/day) administration not only significantly reduced the body weight and ovary weight, but also attenuated the disrupted estrous cycle and decreased the level of testosterone. MV restored the follicular development, especially by increasing the number of corpus luteum and the thickness of the granular layer in young-adult POCS rats. Moreover, metabolomics showed that MV markedly increased the levels of D-Glucose 6-phosphate, lactate and GTP, while decreased the level of pyruvate. Bioinformatic analysis revealed that MV recovered multiple metabolism-related processes including gluconeogenesis, glycolysis and glucose metabolic process. Further real-time quantitative PCR analysis showed that MV upregulated the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Western blotting and immunohistochemistry analysis showed that MV restored the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Collectively, these findings indicated that MV could effectively improve the ovarian microenvironment by upregulating the expression of LDHA, HK2 and PKM2 in granulosa cells and enhancing lactate and energy production, which may contribute to follicle development and ovulation of young-adult PCOS rats.