High correlated color temperature artificial lighting impairs retinal pigment epithelium integrity and chloride ion transport: A potential mechanism for choroidal thinning.

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.

Dual single guide RNAs-mediating deletion of mature myostatin peptide results in concomitant muscle fibre hyperplasia and adipocyte hypotrophy in pigs.

Myostatin (MSTN) is a major gene target for skeletal muscle overgrowth in animals. We hypothesized that deletion of the entire mature peptide encoded by MSTN in pigs would knock out its bioactive form and accordingly stimulate skeletal muscle overgrowth. Thus, we engineered two pairs of single-guide RNAs (sgRNAs) to target exons 1 and 3 of MSTN in primary fetal fibroblasts of Taoyuan black pigs. We found that sgRNAs targeting exon 3, which encodes the mature peptide, had higher biallelic null mutation efficiency than those targeting exon 1. Somatic cell nuclear transfer was conducted using the exon 3 mutation cells as donor cells to generate five cloned MSTN null piglets (MSTN-/-). Growth testing revealed that both the growth rate and average daily weight gain of MST-/- pigs were greater than those of wild-type (MSTN+/+) pigs. Slaughter data demonstrated that the lean ratio of MSTN-/- pigs was 11.3% higher (P < 0.01) while the back-fat thickness was 17.33% lower (P < 0.01) than those of MSTN+/+ pigs. Haematoxylin-eosin staining indicated that the increased leanness of MSTN-/- pigs resulted from muscle fibre hyperplasia rather than hypertrophy.HE staining showed markedly decreased adipocyte size in MSTN-/- pigs. We also critically examined the off-target and random integration by resequencing, which showed that the founder MSTN-/- pigs contained no non-target mutations or exogenous plasmid elements. This study is the first to report the successful knock out of the mature MSTN peptide using dual sgRNA-mediated deletion, leading to the most prominent alteration of meat production traits in pigs published thus far. This new strategy is expected to have a wide impact on genetic improvements in food animals.

Mapping and candidate gene analysis of clustered bud on the main inflorescence in Brassica napus L.

Breeding rapeseed varieties with more main inflorescence siliques is an idea for developing rapeseed varieties that are suitable for light and simplified cultivation. The Brassica napus exhibited cluster bud of the main inflorescence (Bnclib) gene. At the fruiting stage, the main inflorescence had more siliques, higher density, and more main inflorescences. Moreover, the top of the main inflorescence bifurcated. Genetic analysis showed that the separation ratio between Bnclib and the wild type in the F2 generation was 3:1, which indicated that the trait was a single-gene-dominant inheritance. Among the 24 candidate genes, only one gene, BnaA03g53930D, showed differential expression between the groups (False discovery rate, FDR ≤ 0.05, |log2FC|≤ 1). qPCR verification of the BnaA03g53930D gene between Huyou 17 and its Bnclib near-isogenic line showed that BnaA03g53930D was significantly differentially expressed in the stem tissue of Huyou 17 and its Bnclib near-isogenic line (Bnclib NIL). The determination of gibberellin (GA), brassinolide (BR), cytokinin (CTK), jasmonic acid (JA), growth hormone (IAA), and strigolactone (SL) content in the shoot apex of Huyou 17 by Bnclib NIL and wild type showed that all six hormones significantly differed between the Bnclib NIL and Huyou 17. It is necessary to conduct further research on the interactions between JA and the other five hormones and the main inflorescence bud clustering in B. napus.

Deeply Reconstructed Hierarchical Ni-Co Microwire for Flexible Ni-Zn Microbattery with Excellent Comprehensive Performance.

The rise of flexible electronics calls for efficient microbatteries (MBs) with requirements in energy/power density, stability, and flexibility simultaneously. However, the ever-reported flexible MBs only display progress around certain aspects of energy loading, reaction rate, and electrochemical stability, and it remains challenging to develop a micro-power source with excellent comprehensive performance. Herein, a reconstructed hierarchical Ni-Co alloy microwire is designed to construct flexible Ni-Zn MB. Notably, the interwoven microwires network is directly formed during the synthesis process, and can be utilized as a potential microelectrode which well avoids the toxic additives and the tedious traditional powder process, thus greatly simplifying the manufacture of MB. Meanwhile, the hierarchical alloy microwire is composed of spiny nanostructures and highly active alloy sites, which contributes to deep reconstruction (≈100 nm). Benefiting from the dense self-assembled structure, the fabricated Ni-Zn MB obtained high volumetric/areal energy density (419.7 mWh cm-3 , 1.3 mWh cm-2 ), and ultrahigh rate performance extending the power density to 109.4 W cm-3 (328.3 mW cm-2 ). More surprisingly, the MB assembled by this inherently flexible microwire network is extremely resistant to bending/twisting. Therefore, this novel concept of excellent comprehensive micro-power source will greatly hold great implications for next-generation flexible electronics.

Enhanced Formation of 6PPD-Q during the Aging of Tire Wear Particles in Anaerobic Flooded Soils: The Role of Iron Reduction and Environmentally Persistent Free Radicals.

Rapid urbanization drives increased emission of tire wear particles (TWPs) and the contamination of a transformation product derived from tire antioxidant, termed as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), with adverse implications for terrestrial ecosystems and human health. However, whether and how 6PPD-Q could be formed during the aging of TWPs in soils remains poorly understood. Here, we examine the accumulation and formation mechanisms of 6PPD-Q during the aging of TWPs in soils. Our results showed that biodegradation predominated the fate of 6PPD-Q in soils, whereas anaerobic flooded conditions were conducive to the 6PPD-Q formation and thus resulted in a ∼3.8-fold higher accumulation of 6PPD-Q in flooded soils than wet soils after aging of 60 days. The 6PPD-Q formation in flooded soils was enhanced by Fe reduction-coupled 6PPD oxidation in the first 30 days, while the transformation of TWP-harbored environmentally persistent free radicals (EPFRs) to superoxide radicals (O2•-) under anaerobic flooded conditions further dominated the formation of 6PPD-Q in the next 30 days. This study provides significant insight into understanding the aging behavior of TWPs and highlights an urgent need to assess the ecological risk of 6PPD-Q in soils.

Effect of Wearing N95 Mask on the Quality of Chest Compressions in Prehospital Emergency Personnel: A Cross-over Study.

OBJECTIVE: To evaluate the effect of wearing an N95 mask on the quality of chest compression and fatigue of prehospital emergency personnel during cardiopulmonary resuscitation (CPR). METHODS: Twenty-four eligible participants were recruited. Participants' age, sex, height, and weight were recorded. After completing the CPR training and examination, participants were tested twice, wearing surgical mask or an N95 mask, while performing chest compressions for 2 minutes. The quality of chest compression (including compression frequency, depth, rebound, and position) was recorded by the simulator. Borg fatigue scores and physiological parameters (including heart rate, mean arterial pressure, pulse oxygen saturation, and respiratory rate) were recorded before and after chest compressions. RESULTS: Compared to wearing surgical masks, participants wearing N95 masks had significantly lower quality of chest compression, including compression frequency (98.3 ± 4.9 bpm vs 104.0 ± 6.0 bpm, P < 0.001), depth (47.1 ± 4.5 mm vs 50.5 ± 5.4 mm, P < 0.001), and rebound (90.2 ± 2.7% vs 94.3 ± 2.1%, P < 0.001). The compression position was not affected. The period data showed that the difference in compression quality started after 1 minute of compressions. Participants wearing N95 masks had higher Borg fatigue scores [6.1(2) vs 5.1(2), P < 0.001], heart rates (121.2 ± 5.7 bpm vs 109.9 ± 6.0 bpm, P < 0.001), mean arterial pressures (106.3 ± 8.0 mmHg vs 99.0 ± 8.5 mmHg, P = 0.012), and respiratory rates (29.5 ± 2.7 bpm vs 24.7 ± 2.5 bpm, P < 0.001). CONCLUSION: This study showed that the use of an N95 mask by prehospital emergency personnel during the performance of chest compressions resulted in a reduction of compression quality and increased clinician fatigue. There is a need for CPR training for medical personnel wearing personal protective equipment.

Application of a preoperative pain management mode based on instant messaging software in elderly hip fracture patients: a randomized controlled trial.

BACKGROUND: Preoperative analgesia of hip fracture in elderly patients is important, but it is also lacking. In particular, nerve block was not provided in time. In order to provide more effective analgesia, we designed a multimodal pain management mode based on instant messaging software. METHODS: From May to September 2022, a total of 100 patients with unilateral hip fracture aged over 65 were randomly divided into the test group and the control group. Finally, 44 patients in each group completed the result analysis. A new pain management mode was used in the test group. This mode focuses on the full information exchange between medical personnel in different departments, early fascia iliaca compartment block (FICB), and closed-loop pain management. Outcomes include the time when FICB is completed for the first time; The number of cases of FICB completed by emergency doctors; Patients' pain score, pain duration. RESULTS: The time for patients in the test group to complete FICB for the first time was 3.0 [1.925-3.475] h, which was less than the time for patients in the control group (4.0 [3.300-5.275] h). The difference was statistically significant (P < 0.001). Compared with 16 patients in the control group, 24 patients in the test group completed FICB by emergency doctors, and there was no statistical difference between the two groups (P = 0.087). The test group was superior to the control group in the highest NRS score (4.00 [3.00-4.00] vs 5.00 [4.00-5.75]), the duration of the highest NRS score (20.00 [20.00-25.00] mins vs 40.00 [30.00-48.75] mins), and the NRS > 3 time (35.00 [20.00-45.00] mins vs 72.50 [60.00-45.00] mins). The analgesic satisfaction of patients in the test group (5.00 [4.00-5.00]) was also significantly higher than that of the control group (3.00 [3.00-4.00]). The above four indexes were different between the two groups (P < 0.001). CONCLUSIONS: Using instant messaging software, the new model of pain management can enable patients to receive FICB as soon as possible and improve the timeliness and effectiveness of analgesia. TRIAL REGISTRATION: Chinese Clinical Registry Center, ChiCTR2200059013, 23/04/2022.

Construction and validation of a risk prediction model for intraoperative hypothermia in elderly patients undergoing total hip arthroplasty.

AIMS: To construct and validate an intraoperative hypothermia risk prediction model for elderly patients undergoing total hip arthroplasty (THA). METHODS: We collected data from 718 patients undergoing THA in a tertiary hospital from January 2021 to December 2022. Of these patients, 512 were assigned to the modeling group from January 2021 to April 2022, and 206 participants were assigned to the validation group from May 2022 to December 2022. A logistic regression analysis was performed to construct the model. The area under the curve (AUC) was used to test the model's predictive ability. RESULTS: The incidence rate of intraoperative hypothermia was 51.67%. The risk factors entered into the risk prediction model were age, preoperative hemoglobin level, intraoperative blood loss, postoperative hemoglobin level, and postoperative systolic blood pressure. The model was constructed as follows: logit (P) = - 10.118 + 0.174 × age + 1.366 × 1 (preoperative hemoglobin level) + 0.555 × 1 (postoperative hemoglobin level) + 0.009 × 1 (intraoperative blood loss) + 0.066 × 1 (postoperative systolic blood pressure). Using the Hosmer-Lemeshow test, the P value was 0.676 (AUC, 0.867). The Youden index, sensitivity, and specificity were 0.602, 0.790, and 0.812, respectively. The incidence rates of intraoperative hypothermia in the modeling and validation groups were 53.15% and 48.06%, respectively. The correct practical application rate was 89.81%. This model had good application potential. CONCLUSIONS: This risk prediction model has good predictive value and can accurately predict the occurrence of intraoperative hypothermia in patients who undergo THA, which provides reliable guidance for clinical work and has good clinical application value.

TET Family Members Are Integral to Porcine Oocyte Maturation and Parthenogenetic Pre-Implantation Embryogenesis.

The ten-eleven translocation (TET) enzyme family, which includes TET1/2/3, participates in active DNA demethylation in the eukaryotic genome; moreover, TET1/2/3 are functionally redundant in mice embryos. However, the combined effect of TET1/2/3 triple-gene knockdown or knockout on the porcine oocytes or embryos is still unclear. In this study, using Bobcat339, a specific small-molecule inhibitor of the TET family, we explored the effects of TET enzymes on oocyte maturation and early embryogenesis in pigs. Our results revealed that Bobcat339 treatment blocked porcine oocyte maturation and triggered early apoptosis. Furthermore, in the Bobcat339-treated oocytes, spindle architecture and chromosome alignment were disrupted, probably due to the huge loss of 5-hydroxymethylcytosine (5hmC)and concurrent increase in 5-methylcytosine (5mC). After Bobcat339 treatment, early parthenogenetic embryos exhibited abnormal 5mC and 5hmC levels, which resulted in compromised cleavage and blastocyst rate. The mRNA levels of EIF1A and DPPA2 (ZGA marker genes) were significantly decreased, which may explain why the embryos were arrested at the 4-cell stage after Bobcat339 treatment. In addition, the mRNA levels of pluripotency-related genes OCT4 and NANOG were declined after Bobcat339 treatment. RNA sequencing analysis revealed differentially expressed genes in Bobcat339-treated embryos at the 4-cell stage, which were significantly enriched in cell proliferation, cell component related to mitochondrion, and cell adhesion molecule binding. Our results indicated that TET proteins are essential for porcine oocyte maturation and early embryogenesis, and they act by mediating 5mC/5hmC levels and gene transcription.

Systematical analysis of sludge treatment and disposal technologies for carbon footprint reduction.

This study aims to comprehensively analyze the Greenhouse Gases (GHGs) emissions from current sewage sludge treatment and disposal technologies (building material, landfill, land spreading, anaerobic digestion, and thermochemical processes) based on the database of Science Citation Index (SCI) and Social Science Citation Index (SSCI) from 1998 to 2020. The general patterns, spatial distribution, and hotspots were provided by bibliometric analysis. A comparative quantitative analysis based on life cycle assessment (LCA) put forward the current emission situation and the key influencing factors of different technologies. The effective GHG emissions reduction methods were proposed to mitigate climate change. Results showed that incineration or building materials manufacturing of highly dewatered sludge, and land spreading after anaerobic digestion have the best GHG emissions reduction benefits. Biological treatment technologies and thermochemical processes have great potential for reducing GHGs. Enhancement of pretreatment effect, co-digestion, and new technologies (e.g., injection of carbon dioxide, directional acidification) are major approaches to facilitate substitution emissions in sludge anaerobic digestion. The relationship between the quality and efficiency of secondary energy in thermochemical process and GHGs emission still needs further study. Solid sludge products generated by bio-stabilization or thermochemical processes are considered to have a certain carbon sequestration value and can improve the soil environment to control GHG emissions. The findings are useful for future development and processes selection of sludge treatment and disposal facing carbon footprint reduction.

Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose.

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

Transcriptome Profiling Analysis Identifies LCP1 as a Contributor for Chidamide Resistance in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains a significant health problem and carries with it substantial morbidity and mortality. Chidamide is a novel and orally administered histone deacetylase (HDAC) inhibitor and has been demonstrated its anti-tumor efficacy on different kinds of hematological and solid tumors. However, the underlying mechanism of chidamide resistance is still poorly characterized. METHODS: We established chidamide resistant GC cell lines, AGS ChiR and MGC803 ChiR and investigated the toxicologic effects through cell survival, colony formation and flow cytometry assays in vitro, and a subcutaneous xenograft model in vivo. RNA-sequence was then performed to screen chidamide resistance-associated genes between AGS and AGS ChiR cells. The role of Lymphocyte cytosolic protein 1 (LCP1) in chidamide resistance was explored by gain- and loss-of-function analyses. RESULTS: We found that chidamide significantly inhibited cell proliferation and induced the apoptosis in a concentration-dependent manner in wild-type GC cell lines as compared to chidamide resistant cell lines. The transcriptomic profiling, quantitative RT-PCR, and western blot data revealed that LCP1 was upregulated in AGS ChiR cells compared with parental cells. Overexpression of LCP1 conferred and knockdown of LCP1 attenuated the chidamide resistance of GC cells. Epigenetic derepression of LCP1 by chidamide may be a possible reason for the contribution of LCP1 to chidamide resistance. CONCLUSIONS: These findings illustrated that LCP1 may play a chidamide resistance role in GC, suggesting that LCP1 could be a potential target for the therapy of GC combined with chidamide.

Multiple Effects of Humic Components on Microbially Mediated Iron Redox Processes and Production of Hydroxyl Radicals.

Microbially mediated iron redox processes are of great significance in the biogeochemical cycles of elements, which are often coupled with soil organic matter (SOM) in the environment. Although the influences of SOM fractions on individual reduction or oxidation processes have been studied extensively, a comprehensive understanding is still lacking. Here, using ferrihydrite, Shewanella oneidensis MR-1, and operationally defined SOM components including fulvic acid (FA), humic acid (HA), and humin (HM) extracted from black soil and peat, we explored the SOM-mediated microbial iron reduction and hydroxyl radical (•OH) production processes. The results showed that the addition of SOM inhibited the transformation of ferrihydrite to highly crystalline iron oxides. Although FA and HA increased Fe(II) production over four times on average due to complexation and their high electron exchange capacities, HA inhibited 30-43% of the •OH yield, while FA had no significant influence on it. Superoxide (O2•-) was the predominant intermediate in •OH production in the FA-containing system, while one- and two-electron transfer processes were concurrent in HA- and HM-containing systems. These findings provide deep insights into the multiple mechanisms of SOM in regulating microbially mediated iron redox processes and •OH production.

Excited states of chlorophyll a and b in solution by time-dependent density functional theory.

The ground state and excited state electronic properties of chlorophyll (Chl) a and Chl b in diethyl ether, acetone, and ethanol solutions are investigated using quantum mechanical and molecular mechanical calculations with density functional theory (DFT) and time-dependent DFT (TDDFT). Although the DFT/TDDFT methods are widely used, the electronic structures of molecules, especially large molecules, calculated with these methods are known to be strongly dependent on the functionals and the parameters used in the functionals. Here, we optimize the range-separated parameter, µ, of the CAM-B3LYP functional of Chl a and Chl b to reproduce the experimental excitation energy differences of these Chl molecules in solution. The optimal values of µ for Chl a and Chl b are smaller than the default value of µ and that for bacteriochlorophyll a, indicating the change in the electronic distribution, i.e., an increase in electron delocalization, within the molecule. We find that the electronic distribution of Chl b with an extra formyl group is different from that of Chl a. We also find that the polarity of the solution and hydrogen bond cause the decrease in the excitation energies and the increase in the widths of excitation energy distributions of Chl a and Chl b. The present results are expected to be useful for understanding the electronic properties of each pigment molecule in a local heterogeneous environment, which will play an important role in the excitation energy transfer in light-harvesting complex II.

Listeriosis during pregnancy: a retrospective cohort study.

BACKGROUND: Pregnancy-associated listeriosis is a severe infectious disease and potentially leads to fetal/neonatal fatal, while limited information on pregnancy-associated listeriosis is available in China. This study aimed to reveal the clinical characteristics and outcomes of pregnancy-associated listeriosis cases and provide references for treating and managing this disease. METHODS: We performed a retrospective study on maternal and neonatal patients with pregnancy-associated listeriosis. The clinical characteristics of pregnancy-associated listeriosis were studied, and the outcome determinants of neonatal listeriosis were explored. RESULTS: 14 cases of pregnancy-associated listeriosis were identified. The incidence of pregnancy-associated listeriosis in our hospital was 16.69/100,000 births. All of the 14 maternal patients eventually recovered after delivery shortly with no sequelae. None of the 12 mothers who delivered in this hospital received antepartum first-line empirical treatment. Among the 14 neonatal cases, 1 was late-onset listeriosis and 13 were early-onset cases; 11 survived and 3 died. Fatality rates were significantly higher in outborn neonates (P = 0.005). Besides, higher mortality rates were observed in neonates with lower birth weight (P = 0.038), gestational age < 28 weeks (P = 0.056), and Apgar score (5th min) < 5 (P = 0.056), with marginally significant differences. CONCLUSIONS: Pregnancy-associated listeriosis would bring disastrous effects to the neonatal cases, especially to the outborn, low birth weight, and low gestational age of neonates. Timely detection and treatment should be taken seriously for the key neonates. How to early detect L. monocytogenes infected cases, especially in the prenatal stage, remains a serious challenge.

Common clinical features of unilateral retinal pigment epithelium dysgenesis and combined hamartoma of the retina and retinal pigment epithelium.

BACKGROUND: Herein, we report two cases of unilateral retinal pigment epithelium dysgenesis (URPED) in Chinese patients and explore the relationship between URPED and combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). CASE PRESENTATION: The lesion margins in the two cases showed pathognomonic clinical features of URPED, namely, a scalloped reticular margin in hyperplastic retinal pigment epithelium and mild fibrosis. The hypoautofluorescence observed by fundus autofluorescence was inverted compared with that observed by fundus fluorescence angiography. A large amount of fibroglial proliferation and disorganization of the retina involving the whole layer, which are also found in peripapillary CHRRPE, were found in the lesions. CONCLUSIONS: URPED appears to share some clinical features with CHRRPE, and the relationship between URPED and CHRRPE needs further study.

The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy.

BACKGROUND: This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis. METHODS: Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients. RESULTS: Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy. CONCLUSIONS: RPE and choroidal atrophy were found to play an important role in the development of macular caldera.

SLC45A4 promotes glycolysis and prevents AMPK/ULK1-induced autophagy in TP53 mutant pancreatic ductal adenocarcinoma.

BACKGROUND: Somatic mutations of the TP53 gene occur frequently in pancreatic ductal adenocarcinoma (PDA). Solute carrier family 45 member A4 (SLC45A4) is a H+ -dependent sugar cotransporter. The role of SLC45A4 in PDA, especially in TP53 mutant PDA, remains poorly understood. METHODS: We explored the TCGA datasets to identify oncogenes in TP53 mutant PDA. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium], colony formation and 5-ethynyl-2'-deoxyuridine (Edu) assays were performed to investigate the function of SLC45A4 in vitro. Glucose consumption, lactate production and ATP production were detected to evaluate glucose utilization. Extracellular acidification rate and oxygen consumption rate assays were used to evaluate glycolysis and oxidative phosphorylation. The subcutaneous xenotransplantation models were conducted to explore the function of SLC45A4 in vivo. RNA-sequencing and gene set enrichment analysis were employed to explore the biological alteration caused by SLC45A4 knockdown. Western blotting was performed to evaluate the activation of glycolysis, as well as the AMPK pathway and autophagy. RESULTS: SLC45A4 was overexpressed in PDA for which the expression was significantly higher in TP53 mutant PDA than that in wild-type PDA tissues. Moreover, high level of SLC45A4 expression was tightly associated with poor clinical outcomes in PDA patients. Silencing SLC45A4 inhibited proliferation in TP53 mutant PDA cells. Knockdown of SLC45A4 reduced glucose uptake and ATP production, which led to activation of autophagy via AMPK/ULK1 pathway. Deleting SLC45A4 in TP53 mutant HPAF-II cells inhibited the growth of xenografts in nude mice. CONCLUSIONS: The present study found that SLC45A4 prevents autophagy via AMPK/ULK1 axis in TP53 mutant PDA, which may be a promising biomarker and therapeutic target in TP53 mutant PDA.

A Durable Ni-Zn Microbattery with Ultrahigh-Rate Capability Enabled by In Situ Reconstructed Nanoporous Nickel with Epitaxial Phase.

Powering device for miniaturized electronics is highly desired with well-maintained capacity and high-rate performance. Though Ni-Zn microbattery can meet the demand to some extent with intrinsic fast kinetic, it still suffers irreversible structure degradation due to the repeated lattice strain. Herein, a stable Ni-Zn microbattery with ultrahigh-rate performance is rationally constructed through in situ electrochemical approaches, including the reconstruction of nanoporous nickel and the introduction of epitaxial Zn(OH)2 nanophase. With the enhanced ionic adsorption effect, the superior reactivity of the superficial nickel-based nanostructure is well stabilized. Based on facile miniaturization and electrochemical techniques, the fabricated nickel microelectrode exhibits 63.8% capacity retention when the current density is 500 times folded, and the modified hydroxides contribute to the great stability of the porous structure (92% capacity retention after 10 000 cycles). Furthermore, when the constructed Ni-Zn microbattery is measured in a practical metric, excellent power density (320.17 mW cm-2 ) and stable fast-charging performance (over 90% capacity retention in 3500 cycles) are obtained. This surface reconstruction strategy for nanostructure provides a new direction for the optimization of electrode structure and enriches high-performance output units for integrated microelectronics.

Mechanosensitive TRPV4 is required for crystal-induced inflammation.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1ß which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.