Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC). METHODS: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance. RESULTS: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003). CONCLUSIONS: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.

Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and nonesterified fatty acids in dairy cows.

The transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB), and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome, and metabolome of 30 dairy cows during transition (-21, -7, +7, +21 d relative to calving). Then the Bayesian network and 9 machine-learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21, -7, +7 d was higher than +21 d. The plasma concentration of NEFA peaked on +7 d. For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum and in bacterial interactions at +7 d. Conversely, microbial metabolites involved in carbohydrate, lipid, and energy metabolism increased on +7 d. A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (arc strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. The SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB, and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.

Prognostic model of kidney renal clear cell carcinoma using aging-related long noncoding RNA signatures identifies THBS1-IT1 as a potential prognostic biomarker for multiple cancers.

Aging is responsible for the main intrinsic triggers of cancers; however, the studies of aging risk factors in cancer animal models and cancer patients are rare and insufficient to be represented in cancer clinical trials. For a better understanding of the complex regulatory networks of aging and cancers, 8 candidate aging related long noncoding RNAs (CarLncs) identified from the healthy aging models, centenarians and their offsprings, were selected and their association with kidney renal clear cell carcinoma (KIRC) was explored by series of cutting edge analyses such as support vector machine (SVM) and random forest (RF) algorithms. Using data downloaded from TCGA and GTEx databases, a regulatory network of CarLncs-miRNA-mRNA was constructed and five genes within the network were screened out as aging related feature genes for developing KIRC prognostic models. After a strict filtering pipeline for modeling, a formula using the transcript per million (TPM) values of feature genes "LncAging_score = 0.008* MMP11 + 0.066* THBS1-IT1 + (-0.014)* DYNLL2 + (-0.030)* RMND5A+ 0.008* PEG10" was developed. ROC analysis and nomogram suggest our model achieves a great performance in KIRC prognosis. Among the 8 CarLncs, we found that THBS1-IT1 was significantly dysregulated in 12 cancer types. A comprehensive pan-cancer analysis demonstrated that THBS1-IT1 is a potential prognostic biomarker in not only KIRC but also multiple cancers, such as LUSC, BLCA, GBM, LGG, MESO, PAAD, STAD and THCA, it was correlated with tumor microenvironment (TME) and tumor immune cell infiltration (TICI) and its high expression was related with poor survival.

Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape.

Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the STOML3+ cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.

Glutathione inhibited starch digestion: Structural and kinetic analysis of substrate and α-amylase.

Glutathione (GSH) is a natural antioxidant that helps fight free radicals. Whether it will affect the activity of amylase and starch digestion remains unknown. This research disclosed that GSH could interact with starch through hydrogen bonds, which accelerated the swelling of starch granules and promoted the formation of ordered double-helix crystalline, and therefore inhibited starch digestion. Moreover, pig pancreas α-amylase (PPA) which was incubated with GSH displayed a less stable conformation and decreased activity. However, in a crowded media constructed by sodium caseinate (NaCas), an antagonistic effect existed between GSH and NaCas. As the rate and extent of starch digestion have been linked with health aspects, this study suggests that GSH can be used in the formulation of diet foods. It also reminds us to consider the synergistic or antagonistic effects caused by the coexisted components in the complexed food matrix.

Lyophilized bovine acellular tendon linear fiber material for the reconstruction of attachment structure of paraspinous muscles: an animal in vivo study.

Low back pain is common after lumbar spine surgery and the injury from extensive detachment of paraspinal muscles during the surgery may play a vital role. Previously, we prepared a bovine acellular tendon fiber (ATF) material through lyophilization and proved that it could retain its original fibrillar structure and mechanical properties. The objective of this study is to evaluate the effectiveness of this new fiber material used for attachment structure reconstruction of paraspinal muscle. Defect of spinous process, interspinous and supraspinous ligament was established on lumbar spine in rabbit and rat and ATF linear material was implanted to reconstruct the attachment structure. Ultrasound showed the cross-sectional area of the paraspinal muscle in ATF group was larger than that of control group in rats. MRI showed the irregular shape and high signal changes in control group, but regular shape and uniform signal in the ATF group in rabbit. For Electromyogram, the frequency of evoked potential in control group was lower than ATF group and normal rats. HE and Masson staining showed good tissue healing, and immunohistochemical results showed the immune rejection of ATF is significantly lower than that of suture. Reconstruction of the attachment structure of paraspinous muscles with ATF linear material could maintain the morphology, volume and function of paraspinal muscle. ATF material has the potential to be used to manufacture personalized ligaments and other tissue engineering scaffolds. Graphical abstract.

Microbiota-host crosstalk in the newborn and adult rumen at single-cell resolution.

BACKGROUND: The rumen is the hallmark organ of ruminants, playing a vital role in their nutrition and providing products for humans. In newborn suckling ruminants milk bypasses the rumen, while in adults this first chamber of the forestomach has developed to become the principal site of microbial fermentation of plant fibers. With the advent of single-cell transcriptomics, it is now possible to study the underlying cell composition of rumen tissues and investigate how this relates the development of mutualistic symbiosis between the rumen and its epithelium-attached microbes. RESULTS: We constructed a comprehensive cell landscape of the rumen epithelium, based on single-cell RNA sequencing of 49,689 high-quality single cells from newborn and adult rumen tissues. Our single-cell analysis identified six immune cell subtypes and seventeen non-immune cell subtypes of the rumen. On performing cross-species analysis of orthologous genes expressed in epithelial cells of cattle rumen and the human stomach and skin, we observed that the species difference overrides any cross-species cell-type similarity. Comparing adult with newborn cattle samples, we found fewer epithelial cell subtypes and more abundant immune cells, dominated by T helper type 17 cells in the rumen tissue of adult cattle. In newborns, there were more fibroblasts and myofibroblasts, an IGFBP3+ epithelial cell subtype not seen in adults, while dendritic cells were the most prevalent immune cell subtype. Metabolism-related functions and the oxidation-reduction process were significantly upregulated in adult rumen epithelial cells. Using 16S rDNA sequencing, fluorescence in situ hybridization, and absolute quantitative real-time PCR, we found that epithelial Desulfovibrio was significantly enriched in the adult cattle. Integrating the microbiome and metabolome analysis of rumen tissues revealed a high co-occurrence probability of Desulfovibrio with pyridoxal in the adult cattle compared with newborn ones while the scRNA-seq data indicated a stronger ability of pyroxidal binding in the adult rumen epithelial cell subtypes. These findings indicate that Desulfovibrio and pyridoxal likely play important roles in maintaining redox balance in the adult rumen. CONCLUSIONS: Our integrated multi-omics analysis provides novel insights into rumen development and function and may facilitate the future precision improvement of rumen function and milk/meat production in cattle.

Effect of Ionic and Non-Ionic Surfactants on the Pasting Characteristics and Digestive Properties of Regular and Frozen Starch for Oral Delivery.

Starch is an ideal wall material for controlled release in oral delivery systems due to its non-allergic properties, availability, and cheap price. However, because of its poor mechanical behavior and high water permeability, it is necessary to modify the amphiphilic nature of starch. Surfactants are essential components to emulsify the lyophobic food ingredients. However, the interaction of starch with emulsifiers and how they affect the pasting behavior and digestion of starch are not well understood. In this paper, surfactants, such as non-ionic Tween (TW) and ionic sodium fatty acid (NaFA), with varying hydrophobic carbon chain lengths, were selected as model amphiphiles to investigate the structural, pasting, rheological properties and in vitro digestibility of regular and frozen starch samples. The results showed that, in most cases, the addition of TW reduced the viscosity of starch. However, saturated medium-chain NaFA increased the starch viscosity and rheological modulus greatly. Both surfactants inhibited starch digestion. This paper presents a comparative investigation on the effect of ionic and non-ionic surfactant on the structure and properties of corn starch, and therefore the information is useful for structural-based formulation with starch for developing colloidal delivery systems. It is also helpful for developing functional food with controllable digestion properties.

Face Mask-Associated Recurrent Corneal Erosion Syndrome and Corneal Infection.

ABSTRACT: In the current coronavirus disease 2019 (COVID-19) pandemic, important public health measures such as the utilization of face masks has been widely enforced, including community-wide mandatory face mask use. During this period, there have been observations of an increasing number of patients presenting with dry eye symptoms among regular mask users with no history of ocular surface pathology. Individuals have reported being aware of air blowing upward from the mask into their eyes that is likely to increase the evaporation of their tear film leading to ocular irritation. Although face mask use is essential in combatting the COVID-19 pandemic, it is important to recognize the potential effects it may have on ocular health. We report a case of face mask-associated ocular complication. After an initial cornea abrasion from mask use, the patient developed recurrent corneal erosion syndrome that was complicated by microbial keratitis after the enforcement of mandatory mask use in public areas.

A survey of visual impairment and blindness in children attending eight schools for the blind in Myanmar: An update.

Purpose: To determine the causes of visual impairment (VI) and blindness among children in schools for the blind in Myanmar; to identify the avoidable causes of VI and blindness; to provide spectacles, low-vision aids, and ophthalmic treatment where indicated; to provide an update of the 2007 survey performed and identify any major epidemiological changes. Methods: Two hundred and ninety children under 16 years of age from all eight schools for the blind in Myanmar were examined and the data entered into the World Health Organization Prevention of Blindness Examination Record for Childhood Blindness. Results: In total, 271 children (93.4%) were blind (visual acuity [VA] <3/60 in the better eye) and 15 (5.17%) had severe visual impairment (SVI = VA <6/60 to 3/60 in the better eye). Most children had whole globe as the major anatomical site of SVI or blindness (105, 36.6%). The cause was unknown in the majority of these (155, 54.0%). One hundred and twelve children had avoidable causes of blindness and SVI (39.0%). Forty children (13.9%) required an optical device and 10.1% required surgical or medical attention, with a potential for visual improvement through intervention in 3.48%. Conclusion: In all, 39.0% of children had potentially avoidable causes of SVI and blindness with cataracts and measles being the commonest causes. This follow-up survey performed after the first one completed in Myanmar in 2007 demonstrates a change in the major site of abnormality from the cornea to whole globe and a reduction in avoidable blindness but highlights the ongoing burden of measles.

[Effects of Combined Application of Biogas Slurry and Straw on the Migration and Fractions of Soil Heavy Metals in Rice-wheat Rotation System in Coastal Reclamation Areas].

In order to reveal the impact of the application of biogas slurry instead of chemical nitrogen fertilizer on the environmental risk of heavy metals in the soil by returning straw to the field, four treatments, without biogas slurry and without straw applications (CK), biogas slurry application without straw (B), straw application without biogas slurry (S), and biogas slurry combined with straw applications (BS), were applied in a typical coastal reclaimed farmland (rice-wheat rotation) in Jiangsu province. The migration and morphological characteristics of Cu, Zn, Cd, and Pb in different soil layers were observed, and the potential environmental risks were estimated. The results showed that:① The total amounts of Zn and Pb in the surface soils (0-20 cm) in the rice and wheat fields under the BS treatment decreased significantly (P<0.05). The four heavy metals in the paddy soils migrated 6%-11% from the surface to the middle and lower layers (20-60 cm), and Cu, Cd, and Pb in the wheat soils migrate down from the surface by 25% to 33%. This indicated that the combined use of biogas slurry and straw accelerates the vertical downward movement of heavy metals in the surface soil. ② Under the BS treatment, the contents of the weak acid extraction of Cu in the surface soil of the paddy field decreased by 8.8%, and the residual state of Zn, Cd, and Pb decreased by 7.0% to 14.2%. This revealed that Cu was passivated, but Zn, Cd, and Pb tended to be activated. In comparison, the reduction in Cu residues in wheat field surface soil was 2.8 times that of the weak acid extraction, indicating that Cu was activated. Furthermore, the residue state of Cd increased, the weak acid extraction state of Pb decreased, and Cd and Pb were passivated. ③ The ecological risk assessment of heavy metals showed that there is no ecological risk in the soils under the BS treatment, and the risk indices were significantly lower than those of the B and S treatments (P<0.05). Therefore, the combined use of biogas slurry and straw helps to significantly reduce the risk of heavy metal pollution in the soils in the coastal reclamation areas.

Software for Quantifying and Batch Processing Images of Brn3a and RBPMS Immunolabelled Retinal Ganglion Cells in Retinal Wholemounts.

Purpose: The ability to accurately quantify immunohistochemically labeled retinal ganglion cells (RGCs) on wholemounts is an important histopathological determinant in experimental retinal research. Traditionally, this has been performed by manual or semi-automated counting of RGCs. Here, we describe an automated software that accurately and efficiently counts immunolabeled RGCs with the ability to batch process images and perform whole-retinal analysis to permit isodensity map generation. Methods: Retinal wholemounts from control rat eyes, and eyes subjected to either chronic ocular hypertension or N-methyl-D-aspartate (NMDA)-induced excitotoxicity, were labeled by immunohistochemistry for two different RGC-specific markers, Brn3a and RNA-binding protein with multiple splicing (RBPMS). For feasibility of manual counting, images were sampled from predefined retinal sectors, totaling 160 images for Brn3a and 144 images for RBPMS. The automated program was initially calibrated for each antibody prior to batch analysis to ensure adequate cell capture. Blinded manual RGC counts were performed by three independent observers. Results: The automated counts of RGCs labeled for Brn3a and RBPMS closely matched manual counts. The automated script accurately quantified both physiological and damaged retinas. Efficiency in counting labeled RGC wholemount images is accelerated 40-fold with the automated software. Whole-retinal analysis was demonstrated with integrated retinal isodensity map generation. Conclusions: This automated cell counting software dramatically accelerates data acquisition while maintaining accurate RGC counts across different immunolabels, methods of injury, and spatial heterogeneity of RGC loss. This software likely has potential for wider application. Translational Relevance: This study provides a valuable tool for preclinical RGC neuroprotection studies that facilitates the translation of neuroprotection to the clinic.

SURGICAL MANAGEMENT OF TRAUMATIC MACULAR HOLE: Optical Coherence Tomography Features and Outcomes.

PURPOSE: To report the outcomes of eyes receiving surgical management for traumatic macular holes. To describe the preoperative and postoperative optical coherence tomography features of traumatic macular holes and to explore associations between preoperative clinical and optical coherence tomography features, and visual outcome. METHODS: Retrospective study of patients undergoing vitrectomy for traumatic macular hole and entered into the Australian and New Zealand Society of Retinal Specialists surgical registry. Preoperative clinical data, surgical details, and 3-month postoperative outcomes were recorded prospectively. Longer-term outcomes at 12 months were requested retrospectively, as were preoperative and postoperative optical coherence tomography scans. RESULTS: Hole closure was achieved in 91% (21/23) of patients with a single procedure. The average preoperative visual acuity was 20/120. At 3 months postoperatively, the mean visual acuity had improved to 20/70 (P < 0.001), 11/23 (48%) of eyes improved ≥15 letters, and the number of eyes with 20/40 acuity or better increased from 1/23 to 7/23. Eyes with worse visual outcomes (visual acuity < 20/80) had larger holes, worse preoperative acuity, and a greater extent of preoperative ellipsoid band attenuation than those with better postoperative visual acuity. CONCLUSION: Eyes receiving surgical management for traumatic macular hole achieved good anatomical results and approximately half had a substantial improvement in acuity. Ellipsoid band attenuation on preoperative optical coherence tomography and worse preoperative acuity were associated with poorer visual outcomes.

An efficient enantioselective synthesis of (S)-α-methyl-serine methyl ester hydrochloride via asymmetrically catalyzed amination.

We present the synthesis of enantiomerically pure (S)-α-methyl-serine methyl ester hydrochloride from 2-methyl-3-((4-(trifluoromethyl)benzyl)oxy)propanal and di-p-chlorobenzyl azodicarboxylate via asymmetrically catalyzed amination with naphthylalanine derivative catalyst. The application of the organocatalyst of D-3-(1-Naphthyl)-alanine is the key step in the synthesis and ensures the product is obtained with high levels of stereocontrol.