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Atopic dermatitis(AD) is a common inflammatory skin disorder induced by dysfunction of immune suppression, which resembles the mechanism of autoimmune diseases. To explore the association between autoimmune diseases and AD in their children, we linked the birth data from National Birth Registry with National Health Insurance Research Database. Demographic characteristics from 1174,941 parent-child linkages were obtained. There were 312,329 children diagnosed with AD before 5 years old, and they would be compared with the other 862,612 children without AD in the control group. Conditional logistic regression was utilized to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). After adjusting infant’s characteristics, perinatal factors, and other parental diseases, the odds ratio of parental rheumatoid arthritis(RA) was 2.269 (95% CI 1.333–3.861) and parental psoriasis was1.610 (95% CI, 1.094–2.369). Parental allergic diseases such as AD (aOR 2.071, 95% CI 1.952–2.198) and asthma (aOR 1.494, 95% CI 1.400-1.594) were also significant predictors for childhood AD. The subgroup analysis showed significant difference between children’s sex. Parental RA (aOR 3.070, 95% CI, 1.532–6.154) was crucial for boys, while parental psoriasis (aOR 1.945, 95% CI, 1.129–3.350)was a risk factor for girls. In conclusion, parental autoimmune diseases were found to be related to AD in their children before 5 years old. Additionally, there were different risk factors for AD between children’s sex.

Preoperative skin antiseptic preparation is the gold standard for prevention of surgical infection. However, improper use of antiseptics may lead to severe ocular damage. Currently, the most common surgical antiseptics can be divided into aqueous-based and alcohol-based disinfectants, with chlorhexidine and iodine/iodophors being the two major components. Chlorhexidine has a persistent antimicrobial effect and is resistant to neutralization by blood or organic products in surgical wounds. Nevertheless, due to its toxicity to the ears, meninges, and eyes, application of chlorhexidine should be prohibited in these surgical fields. Iodine/iodophor is better tolerated by the ocular surface and is the recommended antiseptic for ophthalmic or head and neck surgeries close to the periocular area. Alcohol is less pricey and has a rapid antiseptic effect, though its desiccating effect and flammability restrict the use in mucosal or laser surgeries. The single or combined use of these antiseptics may inadvertently induce severe ocular damage, especially during time-consuming head and neck surgeries with prone, hyperextension, or lateral tilt positions, or surgeries under general anesthesia. Apart from the choice of antiseptics, appropriate selection and attachment of bio-occlusive dressings are key to avoiding antiseptic-related ocular injuries. In this review, we provided a comprehensive summary of the characteristics of antiseptics used in surgical settings and the possible mechanisms and outcomes of antiseptic-related ocular injuries. The prevention, diagnosis, and acute management of these complications were also discussed.

Clinical registries have been developed for decades in the field of ophthalmology, and they are especially well-suited to the study of keratoplasty practices. A comprehensive donor/recipient registry system can provide insight into donor, recipient, and surgical factors associated with immediate and long-term outcomes and adverse reactions. Furthermore, linkage with demographic databases can elucidate relationships with social determinants of health and potentially shape public policy. The vast sample size and multicenter nature of registries enable researchers to conduct sophisticated multivariate or multilayered analyses. In this review, we aim to emphasize the importance of registry data for keratoplasty practice and 1) summarize the structure of current keratoplasty registries; 2) examine the features and scientific contributions of the registries from Australia, the United Kingdom, Singapore, the Netherlands, Sweden, Eye Bank Association of America, and European Cornea and Cell Transplant registries; 3) compare registry-based studies with large single-site clinical studies; 4) compare registry-based studies with randomized control studies; and 5) make recommendations for future development of keratoplasty registries. Keratoplasty registries have increased our knowledge of corneal transplant practices and their outcomes. Future keratoplasty registry-based studies may be further strengthened by record linkage, data sharing, and international collaboration.

We reported that protein kinase C-η (PKCη) forms a novel (to our knowledge) signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, including suppression of antitumor immunity. However, the importance of PKCη in protective immunity mediated by T effector cells remains unclear. We used mice with germline or conditional Treg-specific deletion of Prkch, the PKCη-encoding gene, to explore CD8+ T cell–dependent antiviral immunity using the lymphocytic choriomeningitis virus Armstrong strain acute infection model as well as the in vitro activation of murine or human CD8+ T cells. Five days following infection, germline Prkch−/− mice displayed enhanced viral clearance compared with control mice. Similarly, Prkch Treg-specific conditional knockout mice also showed improved viral clearance and displayed enhanced expression of granzyme B and IFN-γ by both virus-specific and total CD8+ T cells, demonstrating that enhanced viral clearance in germline Prkch−/− mice is caused by PKCη deficiency in Tregs and the resulting functional defect of Prkch−/− Tregs. In addition, purified Prkch−/− mouse CD8+ T cells as well as PRKCH knockdown human CD8+ T cells displayed intact, or even enhanced, T cell activation in vitro as measured by proliferation and expression of granzyme B and IFN-γ. Thus, global PKCη deletion does not impair overall CD8+ T cell–mediated immunity, including antiviral immunity, implying that selective pharmacological PKCη inhibition could be safely used in vivo to inhibit undesired contact-dependent suppression by Tregs and, thus, enhance tumor-specific and, likely, virus-specific immunity.

Deep Reinforcement learning agent has outperformed human players in many games, such as the Atari 2600 games. In more complicated games, previous related works proposed a curiosity-driven exploration for learning. Nevertheless, it generally requires substantial computational resources to train the agent. We attempt to design a method to assist with our agent to explore the environment. By utilizing prior learned experience more effectively, we develop a new memory replay mechanism, which consists of two modules: Trajectory Replay Module to record the agent moving trajectory information with much less space, and the Trajectory Optimization Module to formulate the state information as a reward. We evaluate our approach with two popular side-scrolling video games: Super Mario Bros and Sonic the Hedgehog. The experiment results show that our method can help the agent explore the environment efficiently, pass through various tough scenarios and successfully reach the goal in most of the testing game levels with merely four workers and of ordinary CPU computational resources for training. The demo videos are at Super Mario Bros and Sonic the Hedgehog.

Aging is a dynamic complex process involving social vulnerability over time. The social vulnerability index (SVI) was developed that predicted adverse health outcomes. This study examined effects between SVI status and two genotypes, apolipoprotein E (ApoE) and Serotonin transporter genotyping (5-HTTLPR), on all-cause mortality. Data from the Social Environment and Biomarkers of Aging Study (SEBAS) were obtained, and SVI was constructed using 32 self-reported items of social determinants. Data from 985 participants (age: 65.73 ± 9.47 years, 54.62% males) were obtained for analysis, and the median SVI was 0.35 (IQR 0.29-0.42) with a near normal distribution. Participants with a higher SVI were more likely to be women and have poor cognitive function, more depressive symptoms and poor physical function. Adjusted for age and sex, each incremental deficit in SVI was associated with a 12% increase in mortality risk (HR: 1.12, 95% CI: 1.04-1.20, p = 0.002). An interaction was found between ApoE and SVI but not 5-HTTLPR. The strata-specific hazard ratio confirmed that associations between SVI and mortality was only in non-e4 carriers (HR: 1.15, 95% CI: 1.07-1.24, p < 0.001), and SVI did not significantly predict mortality among e4 carriers (HR: 0.84, 95% CI: 0.65-1.10). Differential SVI effects on mortality among middle-age and older adults were identified. In conclusion, a higher SVI was associated with all-cause mortality among middle-aged and older adults, and the association was moderated by ApoE genotypes but not 5-HTTLPR. Further study is needed to evaluate the clinical efficacy of healthy aging intervention programs considering gene-environment interactions and social vulnerability.

Background/aimsTo evaluate the utility rate, indication, outcome, and cost of refrigeration and glycerol cryopreservation for storing anterior corneal buttons during endothelial keratoplasty for subsequent use in tectonic lamellar patch grafting.MethodAnterior corneal buttons collected after precutting or prestripping during endothelial keratoplasty from January 2014 to December 2019 were preserved using the following protocol: (1) refrigeration for up to 4 weeks at 4°C in Optisol-GS and (2) glycerol cryopreservation for up to 2 years. The utility rate, outcome and cost of these cryopreserved anterior corneal buttons were retrospectively examined.ResultsDuring the 6-year study period, 26 anterior corneal buttons were refrigerated and 49 were cryopreserved for extended use. The utility rates for the refrigerated and cryopreserved anterior corneal buttons were 69.2% and 73.5%, respectively. Their average preservation periods were 0.53±0.05 and 12.76±0.94 months, respectively. Noninfection-related perforation was the leading indication for using the extendedly preserved anterior corneal buttons. The average postoperative follow-up periods were 10.03±2.91 and 14.35±2.17 months for refrigerated and cryopreserved anterior corneal buttons. Secondary keratoplasty was required by 7 of 18 (38.9%) and 6 of 36 (16.7%) patients receiving refrigerated and cryopreserved anterior corneal buttons, respectively. None of our patients developed graft infection from donor tissues.ConclusionCryopreservation can safely extend the utility of anterior corneal buttons. This method not only reduced the wastage of the limited donor tissue but also was cost-effective.

Purpose To investigate the demographics, risk factors, microbiology, and resistance pattern at a tertiary hospital and to detect the shifting trend over 2 decades. Design A retrospective observational case series. Methods We reviewed all records of patients with microbial keratitis (MK) that were hospitalized in National Taiwan University Hospital between 2007 and 2016. Demographics, predisposing factors, pathogens, and clinical courses were compared to our previous study conducted from 1992 to 2001. Antibiotic susceptibility was compared with those conducted from 1994 to 2005. Results The percentage of patients 60 years and older in the MK population was increasing (P = 2.1E-21). The proportion of trauma-related MK declined while MK related to chronic ocular or systemic disorders rose. The prevalence of nontuberculous mycobacteria (NTM) showed a decreasing trend (P = .0032), whereas Microsporidia has been increasingly detected. The 2 most common bacterial isolates were Pseudomonas aeruginosa (35.2%) and Staphylococcus species (13.2%). Management of these infection did not differ in common pathogens between the 2 decades. The susceptibility of Staphylococcus species to oxacillin reduced significantly (P = .002) and there was an increase in methicillin-resistant Staphylococcus aureus keratitis. Conclusions Contact lens wear remained the most common predisposing factor, with Pseudomonas species as the major pathogen. However, chronic disorder–related MK was on the rise along with an increasing trend of oxacillin resistance in Staphylococcus species. We found a decreasing trend in NTM keratitis while Microsporidia keratitis was considered as an emerging ocular disease. Though gram-negative isolates remained susceptible to all antibiotics tested, antibiotic resistance was more common in gram-positive isolates.

Heating ventilation and air conditioning (HVAC) accounts for approximately 50% of the total energy consumption of buildings. Therefore, many studies have been focused on the simulation and optimal control of HVAC power consumption or the prediction of energy consumption through the construction of energy consumption models and the improvement of HVAC power consumption through energy management methods. The prediction of energy consumption by optimal energy-saving control or energy baseline is dependent on an accurate energy consumption model, however, the accuracy of the energy consumption model is influenced by the model variables. In addition, different operating periods and load conditions also lead to different changes in energy consumption, which will affect the accuracy of optimal energy consumption control or prediction of energy consumption. The present study proposes a method to enhance the accuracy and sensitivity of HVAC power consumption prediction, which involves the use of a clustering technique to locate clusters with similar information within hourly data, the construction of energy consumption models by converting the clustered hourly data into monthly data, and the application of the proposed Naïve Bayes classifier to classify hourly data under different operating conditions into the energy consumption model with the smallest prediction error. A multiple variable regression model and an artificial neural network (ANN) model were compared with the models developed in the present study, and the normalized mean bias error (NMBE) and the coefficient of variation of the root mean squared error (Cv-RMSE) were used as criteria for the predicted energy consumption values.

The study aims to evaluate the therapeutic effects of dermatologic tacrolimus ointment on eyelids to treat refractory vernal keratoconjunctivitis (VKC). This institutional study examined the effects of steroid treatment for 10 patients diagnosed with severe VKC refractory to steroid treatment. Patients received 0.1% dermatologic topical tacrolimus treatment on their eyelids once or twice daily for concomitant atopic dermatitis. The therapeutic outcomes were evaluated according to change in severity of clinical findings recorded with serial external ocular photography and change in requirement for steroid treatment. Clinical signs and symptoms improved substantially after tacrolimus treatment. Significant reduction in size of papillae, decrease of discharge, improvement in hyperemia, and shield ulcer healing with re-epithelization were observed in all patients. Six out of 10 (60%) patients did not receive steroid treatment. Long-term maintenance of tacrolimus was required to prevent episodic exacerbation. Patients’ only treatment-related complaints were of mild burning sensations during medication application to eyelids, and this sensation disappeared a few days after treatment. Application of 0.1% dermatologic tacrolimus ointment to eyelids is effective and safe in the treatment of refractory VKC in patients with concomitant atopic dermatitis. This treatment may serve as a substitute for or decrease the requirement of steroid treatment.

Biocompatible and highly porous network hydrogel scaffolds were fabricated for the development of artificial cornea (AC) periphery/skirt that could be used to enhance the long-term retention of the implants. In this study, a series of hydrogel scaffolds for this application was fabricated from the photo-polymerization of a mixture of poly(ethylene glycol) (PEG)- and poloxamer (P407)-based macromer solutions in dichloromethane in which solvent-induced phase separation (SIPS) arose to form scaffolds with macroporous structure and high water content. The overall porosity ranging from 20% to 75% and open/closed pore structure of the hydrogel scaffolds could be finely tuned by varying the ratio of P407/PEG in the macromer solution and solvent type. The total porosity and open-cell structure of the macropores in the synthesized hydrogel scaffolds affected the swelling behavior, dynamic properties such as the storage moduli of the hydrogels as well as their degradation rates. Based on the subcutaneous implantation in rats, superporous hydrogel scaffolds induced the formation of thinner fibrous capsules around the implants and showed less inflammatory reaction, suggesting that the hydrogel scaffolds made from SIPS exhibited good cytocompatibility. The combined results of swelling ratio, porosity, physical strength and subcutaneous implant tests indicated that the superporous hydrogels with porosity >50% showed potentials to be used for cornea periphery application.

In this study, a series of alcohol-soluble cross-linked block copolymers (BCPs) consisting of poly(n-butyl acrylate) (poly(nBA)) and poly(N-vinyl-1,2,4-triazole) (poly(NVTri)) blocks with different individual functions and lengths are designed and developed. These presynthesized cross-linked BCPs (PBAn–Trim) were, for the first time, revealed to exhibit many advantages in serving as the electron-extraction layer (EEL) for organic photovoltaics (OPVs). The cross-linked BCPs possessed intense ionic functionality, showing well capability to form effective interfacial dipoles at the indium tin oxide interface to facilitate the charge extraction at the corresponding interface. Furthermore, it also consisted a core–shell structure, wherein the polar poly(NVTri) core was well protected by the poly(nBA) shell to endow improved robustness against solvent erosion and thermal/photo inputs. Consequently, the PBA70–Tri30 device yielded a decent power conversion efficiency of 8.03% with a Voc of 0.83 V, much exceeding ...

BackgroundThis study examined whether corneas from bacteremic donors could be used for corneal transplant.MethodsCorneas donated to the National Eye Bank of Taiwan between 1 January 2014 and 30 June 2017 were included in this study. All the corneas had corneoscleral rim cultures during the retrieval process and were hypothermic preserved in the Optisol-GS storage medium. A microbial work-up flow chart was used for the sterility check of all grafts. Bacteremic donors were defined as those whose last blood culture before corneal donation was positive. The microbial contamination rates, the endothelial cell densities, the tissue utility rates and early complications after transplants were compared between the corneas from bacteremic versus non-bacteremic donors.Results697 corneas from 356 donors were analysed, 70 of which were from bacteremic donors. The microbial contamination rates of the corneas from bacteremic and non-bacteremic donors (7.1% vs 9.1%)(p=0.30) were close. None of the contaminated corneas grew the same bacterial strains as those from their blood cultures. The corneas from bacteremic donors and non-bacteremic donors have similar endothelial cell densities (2931±297 cells/mm2 vs 2903 ± 470 cells/mm2) (p=0.63). Corneas from bacteremic and non-bacteremic donors shared a similar utility rate (98.6% vs 99.4%)(p=0.41). None of the corneas caused infectious complications after transplants.ConclusionOur study showed that corneas from bacteremic and non-bacteremic donors have equally low contamination rates and are of the same quality in terms of endothelial cell density and safety.

Purpose To develop and compare deep learning (DL) algorithms to detect keratoconus on the basis of corneal topography and validate with visualization methods. Methods We retrospectively collected corneal topographies of the study group with clinically manifested keratoconus and the control group with regular astigmatism. All images were divided into training and test datasets. We adopted three convolutional neural network (CNN) models for learning. The test dataset was applied to analyze the performance of the three models. In addition, for better discrimination and understanding, we displayed the pixel-wise discriminative features and class-discriminative heat map of diopter images for visualization. Results Overall, 170 keratoconus, 28 subclinical keratoconus and 156 normal topographic pictures were collected. The convergence of accuracy and loss for the training and test datasets after training revealed no overfitting in all three CNN models. The sensitivity and specificity of all CNN models were over 0.90, and the area under the receiver operating characteristic curve reached 0.995 in the ResNet152 model. The pixel-wise discriminative features and the heat map of the prediction layer in the VGG16 model both revealed it focused on the largest gradient difference of topographic maps, which was corresponding to the diagnostic clues of ophthalmologists. The subclinical keratoconus was positively predicted with our model and also correlated with topographic indexes. Conclusions The DL models had fair accuracy for keratoconus screening based on corneal topographic images. The visualization mentioned in the current study revealed that the model focused on the appropriate region for diagnosis and rendered clinical explainability of deep learning more acceptable. Translational relevance These high accuracy CNN models can aid ophthalmologists in keratoconus screening with color-coded corneal topography maps.

PURPOSE: To report a case of bilateral non-tuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE) that was successfully treated with oral and topical fortified antibiotics. METHODS: Case report and literature review. RESULTS: An otherwise healthy 21-year-old woman presented with culture-proven bilateral Mycobacterium abscessus keratitis 8 days after undergoing SMILE, showing multiple white stromal infiltrates in the interface in both eyes. Progressive, diffuse flap edema followed by pocket abscess, exudation in the anterior chamber, granulation tissue formation in the pocket, intrastromal neovascularization, and eventually partial resolution of corneal opacity were noted after topical and oral antibiotic treatment for 6 months. Her corrected distance visual acuity was 20/32 and 20/50 in the right and left eyes, respectively, 12 months after initial presentation. CONCLUSIONS: This is the first report of successful medical management of bilateral non-tuberculous mycobacterial keratitis after SMILE. The manifestations are different from and even more difficult to treat than those of keratitis after LASIK. [ J Refract Surg. 2018;34(9):633–636.]

Hung et al. combine in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling to show that the activation of TLR8, TLR7, or TLR3 results in dendritic shortening and that TLR7 and TLR3 but not TLR8 also control axonal growth. In-depth transcriptomic analyses show that TLRs use different downstream pathways to control neuronal morphology despite signaling through the same adapter, MYD88., Neuroinflammation is associated with diverse neurological disorders. Endosomal Toll-like receptors (TLRs) including TLR3, TLR7, and TLR8 cell-autonomously regulate neuronal differentiation. However, the mechanisms by which these three TLRs affect neuronal morphology are unclear. In this study, we compare these TLRs in mouse neurons. By combining in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling, we show that TLR8, TLR7, and TLR3 promote dendritic pruning via MYD88 signaling. However, they induce different transcriptomic profiles related to innate immunity, signaling, and neuronal development. The temporal expression patterns and the effects on neuronal morphology are not identical upon activation of these endosomal TLRs. Pathway analyses and in vitro studies specifically implicate mitogen-activated protein kinase signaling in TLR8-mediated dendritic pruning. We further show that TLR8 is more critical for dendritic arborization at a late development stage in vivo. The activation of TLR8, TLR7, or TLR3 results in dendritic shortening, and TLR7 and TLR3 but not TLR8 also control axonal growth. In-depth transcriptomic analyses show that TLRs use different downstream pathways to control neuronal morphology, which may contribute to neuronal development and pathological responses.

Older adults with multiple complex care needs tend to receive fragmented care that may jeopardize their quality of life (QoL) and health outcomes. This study evaluated the determinants of improved QoL among integrated outpatient service recipients with multimorbidity.We conducted a retrospective cohort study of integrated geriatric outpatient services (IGOS) at a tertiary medical center in Taiwan. Data from 2018 to 2019 were retrieved. All patients underwent comprehensive geriatric assessment, which included demographic information, serial functional assessments, and assessment for QoL. QoL was reassessed through a telephone survey 6 months after the patients' first visit to IGOS. Factors associated with the interval changes in QoL were identified using multivariate logistic regression.Data from 995 patients receiving IGOS (mean age: 82.21 ± 7.96 years, 54.5% males) were analyzed. An overall mean improvement in QoL was noted (EQ-5D index: +0.055±0.26, p0.001) while 747 recipients reported maintained or improved QoL. The results of the multivariate logistic regression showed that poorer nutritional status (OR = 1.56, 95% CI: 1.07-2.28), depressive symptoms (OR = 1.99, 95% CI: 1.38-2.86), and frailty (OR = 1.66, 95% CI: 1.10-2.52) were independent risk factors for poorer QoL after adjustment for baseline QoL.Integrated outpatient services improved the quality of life of older adults with multimorbidity. Those with poorer nutritional status, depressive symptoms and frailty were less likely to show improvement in their QoL.

Objective: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. Methods: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice. Results: We found that Aim2 knockout mitigates Aβ deposition in the cerebral cortex and hippocampus of 5XFAD mice. The activation of microglial cells is also reduced in Aim2-/-;5XFAD brains compared with 5XFAD brains. However, Aim2 knockout does not improve memory and anxiety phenotypes of 5XFAD mice in an open field, cued Y-maze, or Barnes maze. Compared with 5XFAD mice, Il-1 expression levels are not reduced in Aim2-/-;5XFAD mice. Unexpectedly, Il-6 and Il-18 expression levels in 5XFAD brains were further increased when Aim2 was deleted. Thus, inflammatory cytokine expression in 5XFAD brains is upregulated by Aim2 deletion through an unknown mechanism. Conclusion: Although Aim2 knockout mitigates Aβ deposition and microglial activation, Aim2 deletion does not have a beneficial effect on the spatial memory or cytokine expression of 5XFAD mice. Our findings suggest that Aβ aggregation and microglial activation may not always be correlated with the expression of inflammatory cytokines or cognitive function of 5XFAD mice. Our study also implies that different inflammasomes likely perform distinct roles in different physiological and/or pathological events.

Viral infection during fetal or neonatal stages increases the risk of developing neuropsychiatric disorders such as schizophrenia and autism spectrum disorders. Although neurons express several key regulators of innate immunity, the role of neuronal innate immunity in psychiatric disorders is still unclear. Using cultured neurons and in vivo mouse brain studies, we show here that Toll‐like receptor 3 (TLR3) acts through myeloid differentiation primary response gene 88 (MYD88) to negatively control Disrupted in schizophrenia 1 ( Disc1 ) expression, resulting in impairment of neuronal development. Cytokines are not involved in TLR3‐mediated inhibition of dendrite outgrowth. Instead, TLR3 signaling suppresses expression of several psychiatric disorder‐related genes, including Disc1 . The impaired dendritic arborization caused by TLR3 activation is rescued by MYD88 deficiency or DISC1 overexpression. In addition, TLR3 activation at the neonatal stage increases dendritic spine density, but narrows spine heads at postnatal day 21 (P21), suggesting a long‐lasting effect of TLR3 activation on spinogenesis. Our study reveals a novel mechanism of TLR3 in regulation of dendritic morphology and provides an explanation for how environmental factors influence mental health.

We reported that protein kinase C-eta (PKCη) forms a novel signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, including suppression of anti-tumor immunity. However, the importance of PKCη in protective immunity mediated by T effector (Teff) cells remains unclear. We used mice with germline or conditional, Treg-specific deletion of Prkch, the PKCη-encoding gene, to explore CD8(+) T cell-dependent antiviral immunity using the lymphocytic choriomeningitis virus Armstrong strain acute infection model, as well as the in vitro activation of murine or human CD8(+) T cells. Five days following infection, germline Prkch(−/−) mice displayed enhanced viral clearance compared to control mice. Similarly, Prkch Treg-specific conditional knockout (cKO) mice also showed improved viral clearance and displayed enhanced expression of granzyme B (GzmB) and interferon-γ (IFNγ) by both virus-specific and total CD8(+) T cells, demonstrating that enhanced viral clearance in germline Prkch(−/−) mice is caused by PKCη deficiency in Tregs and the resulting functional defect of Prkch(−/−) Tregs. In addition, purified Prkch(−/−) mouse CD8(+) T cells as well as PRKCH knockdown human CD8(+) T cells displayed intact, or even enhanced, T cell activation in vitro as measured by proliferation and expression of GzmB and IFNγ. Thus, global PKCη deletion does not impair overall CD8(+) T cell-mediated immunity, including antiviral immunity, implying that selective pharmacological PKCη inhibition could be safely used in vivo to inhibit undesired contact-dependent suppression by Tregs and, thus, enhance tumor-specific and, likely, virus-specific immunity.

The objective of this study was to develop a heating, ventilation, and air conditioning (HVAC) system optimization control strategy involving fan coil unit (FCU) temperature control for energy conservation in chilled water systems to enhance the operating efficiency of HVAC systems. The proposed control strategy involves three techniques, which are described as follows. The first technique is an algorithm for dynamic FCU temperature setting, which enables the FCU temperature to be set in accordance with changes in the outdoor temperature to satisfy the indoor thermal comfort for occupants. The second technique is an approach for determining the indoor cold air demand, which collects the set FCU temperature and converts it to the refrigeration ton required for the chilled water system, this serves as the control target for ensuring optimal HVAC operation. The third technique is a genetic algorithm for calculating the minimum energy consumption for an HVAC system. The genetic algorithm determines the pump operating frequency associated with minimum energy consumption per refrigeration ton to control energy conservation. To demonstrate the effectiveness of the proposed HVAC system optimization control strategy combining FCU temperature control, this study conducted a field experiment. The results revealed that the proposed strategy enabled an HVAC system to achieve 39.71% energy conservation compared with an HVAC system operating at full load.

Corneal endothelial dysfunction causes corneal edema and severe visual impairments that may lead to permanent blindness. Although corneal endothelial keratoplasty is currently the treatment-of-choice to restore vision, it faces several difficulties, including worldwide shortage of donor corneas, progressive loss of endothelial cells after surgery, and extensive damage of endothelial cells during surgical manipulation. With further understanding of the corneal endothelial cell biology and advances in the field of pharmacological treatment, tissue engineering, cell or stem cell therapy, different strategies have been developed to treat corneal endothelial disorders.

In this study, a series of alcohol-soluble cross-linked block copolymers (BCPs) consisting of poly( n-butyl acrylate) (poly( nBA)) and poly( N-vinyl-1,2,4-triazole) (poly(NVTri)) blocks with different individual functions and lengths are designed and developed. These presynthesized cross-linked BCPs (PBA