Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney.

The functional and structural changes in the proximal tubule play an important role in the occurrence and development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead to changes in the state of tubular epithelial cells (TECs), and among all the disturbances in metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production of mitochondrial reactive oxygen species (mtROS), is considered one of the primary factors causing diabetic tubular injury. Most studies have discussed how altered metabolic flux drives mitochondrial oxidative stress during DKD. In the present study, we focused on targeting mitochondrial damage as an upstream factor in metabolic abnormalities under diabetic conditions in TECs. Using SS31, a tetrapeptide that protects the mitochondrial cristae structure, we demonstrated that mitochondrial oxidative damage contributes to TEC injury and lipid peroxidation caused by lipid accumulation. Mitochondria protected using SS31 significantly reversed the decreased expression of key enzymes and regulators of fatty acid oxidation (FAO), but had no obvious effect on major glucose metabolic rate-limiting enzymes. Mitochondrial oxidative stress facilitated renal Sphingosine-1-phosphate (S1P) deposition and SS31 limited the elevated Acer1, S1pr1 and SPHK1 activity, and the decreased Spns2 expression. These data suggest a role of mitochondrial oxidative damage in unbalanced lipid metabolism, including lipid droplet (LD) formulation, lipid peroxidation, and impaired FAO and sphingolipid homeostasis in DKD. An in vitro study demonstrated that high glucose drove elevated expression of cytosolic phospholipase A2 (cPLA2), which, in turn, was responsible for the altered lipid metabolism, including LD generation and S1P accumulation, in HK-2 cells. A mitochondria-targeted antioxidant inhibited the activation of cPLA2f isoforms. Taken together, these findings identify mechanistic links between mitochondrial oxidative metabolism and reprogrammed lipid metabolism in diabetic TECs, and provide further evidence for the nephroprotective effects of SS31 via influencing metabolic pathways.

Multi-omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma.

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.

Growth, spectroscopy and SESAM mode-locking of a "mixed" Yb:Ca(Gd,Y)AlO4 disordered crystal.

We present the growth, spectroscopy, continuous-wave (CW) and passively mode-locked (ML) operation of a novel "mixed" tetragonal calcium rare-earth aluminate crystal, Yb3+:Ca(Gd,Y)AlO4. The absorption, stimulated-emission, and gain cross-sections are derived for π and σ polarizations. The laser performance of a c-cut Yb:Ca(Gd,Y)AlO4 crystal is studied using a spatially single-mode, 976-nm fiber-coupled laser diode as a pump source. A maximum output power of 347 mW is obtained in the CW regime with a slope efficiency of 48.9%. The emission wavelength is continuously tunable across 90 nm (1010 - 1100 nm) using a quartz-based Lyot filter. With a commercial SEmiconductor Saturable Absorber Mirror to initiate and maintain ML operation, soliton pulses as short as 35 fs are generated at 1059.8 nm with an average output power of 51 mW at ∼65.95 MHz. The average output power can be scaled to 105 mW for slightly longer pulses of 42 fs at 1063.5 nm.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

Separating Charge Centers of Chain Segments in Dielectric Elastomer through Steric Hindrance Engineering.

Theoretically, separating the positive and negative charge centers of the chain segments of dielectric elastomers (DEs) is a viable alternative to the conventional decoration of chain backbone with polar handles, since it can dramatically increase the dipole vector and hence the dielectric constant (ε') of the DEs while circumvent the undesired impact of the decorated polar handles on the dielectric loss (tan δ). Herein, a novel and universal method is demonstrated to achieve effective separation of the charge centers of chain segments in homogeneous DEs by steric hindrance engineering, i.e., by incorporating a series of different included angle-containing building blocks into the networks. Both experimental and simulation results have shown that the introduction of these building blocks can create a spatially fixed included angle between two adjacent chain segments, thus separating the charge center of the associated region. Accordingly, incorporating a minimal amount of these building blocks (≈5 mol%) can lead to a considerably sharp increase (≈50%) in the ε' of the DEs while maintaining an extremely low tan δ (≈0.006@1 kHz), indicating that this methodology can substantially optimize the dielectric performance of DEs based on a completely different mechanism from the established methods.

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study.

BACKGROUND: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. METHODS: This retrospective cohort study included 248 children with asthma (aged 4-11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test. RESULTS: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082-2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365-0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170-2.305) and with worse asthma control (OR 3.893, 95% CI 1.699-8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. CONCLUSIONS: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Effect of percutaneous vertebroplasty versus percutaneous kyphoplasty on post-operative wound pain in patients with osteoporotic vertebral compression fractures.

This research is intended to evaluate the efficacy of percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in osteoporotic vertebral compression fracture (OVCF), which is associated with post-operative pain. Eligible studies were screened by searching multiple databases and sources such as PubMed, Cochrane and EMBASE for search terms updated to October 2023, and relevant literature sources were searched. Randomized, controlled, prospective or retrospective, and cohort studies were eligible. For the analysis of the primary results, an analysis of the data was carried out, such as mean difference (MD) or odds ratio (OR), and 95% confidence interval (CI). In the present research, 1933 research was screened in 4 databases, and 30 articles were chosen to be examined under strict exclusion criteria. No statistical significance was found in the use of bone cement in the PVP group and PKP (MD, -0.60; 95% CI, -1.40, 0.21, p = 0.15); PKP was associated with a reduced risk of cement leak compared with PVP group (OR, 2.18; 95% CI, 1.38, 3.46, p = 0.0009); no statistical significance was found in the wound VAS score in PVP operation compared with that of PKP (MD, 0.16; 95% CI, -0.07, 0.40, p = 0.17); no statistical significance was found between the time of PVP operation and the time of PKP operation (MD, -2.65; 95% CI, -8.91, 3.60, p = 0.41). Compared with PVP technology, the PKP treatment of osteoporotic vertebral compression fractures reduces post-operative cement leakage, but there is no significant difference in the number of operative cement and wound VAS after operation. Nor did there appear to be a statistically significant difference in time between the two operations.

Sex and molecular differences in cardiovascular parameters at peak influenza disease in mice.

There is a growing interest in the detection of subtle changes in cardiovascular physiology in response to viral infection to develop better disease surveillance strategies. This is not only important for earlier diagnosis and better prognosis of symptomatic carriers but also useful to diagnose asymptomatic carriers of the virus. Previous studies provide strong evidence of an association between inflammatory biomarker levels and both blood pressure (BP) and heart rate (HR) during infection. The identification of novel biomarkers during an inflammatory event could significantly improve predictions for cardiovascular events. Thus, we evaluated changes in cardiovascular physiology induced in A/Puerto Rico/8/34 (PR8) influenza infections in female and male C57BL/6J mice and compared them with the traditional method of influenza disease detection using body weight (BW). Using radiotelemetry, changes in BP, HR, and activity were studied. Change in BW of infected females was significantly decreased from 5 to 13 days postinfection (dpi), yet alterations in normal physiology including loss of diurnal rhythm and reduced activity was observed starting at about 3 dpi for HR and 4 dpi for activity and BP; continuing until about 13 dpi. In contrast, males had significantly decreased BW 8 to 12 dpi and demonstrated altered physiological measurements for a shorter period compared with females with a reduction starting at 5 dpi for activity, 6 dpi for BP, and 7 dpi for HR until about 12 dpi, 10 dpi, and 9 dpi, respectively. Finally, females and males exhibited different patterns of inflammatory maker expression in lungs at peak disease by analyzing bulk RNA-sequencing data for lungs and Bio-plex cytokine assay for blood collected from influenza-infected and naïve C57BL/6J female and male mice at 7 dpi. In total, this study provides insight into cardiovascular changes and molecular markers to distinguish sex differences in peak disease caused by influenza virus infection.NEW & NOTEWORTHY This study performed longitudinal cardiovascular measurements of influenza viral infection and identified sex difference in both physiological and molecular markers at peak disease.

Single-cell RNA sequencing reveals the heterogeneity and microenvironment in one adenoid cystic carcinoma sample.

Adenoid cystic carcinoma (ACC) is one of the most common malignancy of the major salivary glands with a high recurrence rate and poor prognosis. Determining tumor heterogeneity and factors in the microenvironment may provide novel therapeutic targets for ACC. We performed single-cell RNA sequencing of one ACC sample and normal salivary gland tissues from a patient to analyze tumor heterogeneity, immunosuppressive landscape, and intercellular communication networks. The heterogeneity of epithelial cells in ACC tissues was significantly higher compared with that in normal tissues, whereas immune cells were almost absent. We found four malignant cell clusters in ACC and explored their characteristics and function. In tumor tissues, CD8 + cytotoxic T cells and CD4 + T helper cells were significantly decreased, whereas IgA + plasma cells were absent. There were two clusters of macrophages, one representing IL1B macrophages and the other consisted of a cluster of macrophages associated with the epithelial mesenchymal transition (EMT). Both were significantly different from the normal tissue composition. In addition, the communication between epithelial cells and other cells in the tumor tissue was enhanced. MIF-CD74 and APP-CD74 were significantly upregulated. We comprehensively described the heterogeneity of ACC and the tumor microenvironment (TME) from a single cell perspective including cell characteristics, immune cell infiltration, and cell communication. CLINICAL RELEVANCE: This study provided further insights into ACC and may lead to new treatment strategies.

Stretchable Oxygen-Tolerant Sensor Based on a Single-Atom Fe-N4 Electrocatalyst for Observing the Role of Oxidative Stress in Hypertension.

Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.

Magneto-Nanomechanical Array Biosensor for Ultrasensitive Detection of Oncogenic Exosomes for Early Diagnosis of Cancers.

Exosomes are a class of nanoscale vesicles secreted by cells, which contain abundant information closely related to parental cells. The ultrasensitive detection of cancer-derived exosomes is highly significant for early non-invasive diagnosis of cancer. Here, an ultrasensitive nanomechanical sensor is reported, which uses a magnetic-driven microcantilever array to selectively detect oncogenic exosomes. A magnetic force, which can produce a far greater deflection of microcantilever than that produced by the intermolecular interaction force even with very low concentrations of target substances, is introduced. This method reduced the detection limit to less than 10 exosomes mL-1 . Direct detection of exosomes in the serum of patients with breast cancer and in healthy people showed a significant difference. This work improved the sensitivity by five orders of magnitude as compared to that of traditional nanomechanical sensing based on surface stress mode. This method can be applied parallelly for highly sensitive detection of other microorganisms (such as bacteria and viruses) by using different probe molecules, which can provide a supersensitive detection approach for cancer diagnosis, food safety, and SARS-CoV-2 infection.

Self-imaging-based high-power all-fiber coherent combiners: fabrication and preliminary demonstration.

Self-imaging combiners can achieve near-perfect filled-aperture coherent beam combination in an all-fiber format with a high-power operation capability. In this Letter, the fabrication of proposed self-imaging combiners is presented, along with a demonstration of a 2 × 2 configuration that uses commercially available large-mode-area fibers, glass tube and square-core fiber. Two types of self-imaging combiners have been fabricated using polarization-maintaining fibers and non-polarization-maintaining fibers, respectively, and these have been tested in an all-fiber coherent beam combination system. Preliminary results reveal that non-polarization-maintaining fibers can achieve better positioning precision, and a maximal combining efficiency of 52.7% has been achieved. The deviation of the demonstrated combining efficiency from the theoretical prediction is mainly attributed to the distortion of the fiber bundle and square-core output fiber, which can be further improved by refining the fabrication process and employing specially developed square-core fiber with better geometrical precision. To the best of the authors' knowledge, this is the first validation of all-fiber coherent beam combining based on the self-imaging effect.

A New Molecular Mechanism for Understanding the Actuated Strain of Dielectric Elastomers and Their Impacts.

Dielectric elastomers (DEs) are a special material that deform responding to an electric field. The induced strain is known as actuated strain (AS). This phenomenon is totally different from electrostriction, for there is no crystal lattice in elastomers and the AS of DEs is much greater. The most accepted mechanism holds the view that the AS of DEs is induced by the Maxwell stress. According to this mechanism, materials exhibiting similar ratios of permittivity and Young's modulus should have similar ASs, while the experimental AS isn't relevant to the ideal value, contradicting this mechanism. The direction of uniaxial pre-strained DE's AS cannot be explained by this mechanism either. The electric field and DE are only regarded as a source of stress and a deformable body respectively in this mechanism, which ignores the interaction between those two. Recently, a new molecular mechanism for AS is proposed, in which the electric field first orient dipoles of chains, therefore the conformation of chains will be changed, finally leading to AS. With thermodynamical derivation and experiment, entropy-dominated elasticity is found to account for more during AS. This mechanism is systematically introduced in this perspective and presents current challenges and outlooks of DE.

Molecular dynamics simulation of the impact of the surface topology of carbon black on the mechanical properties of elastomer nanocomposites.

Carbon black has always played a pivotal role in reinforcing elastomers because it remarkably improves the mechanical properties. The reinforcing effect of carbon black is influenced by its grades, which mainly depend on the difference in the structure of the carbon black particles. Despite many traditional experiments on the performance of carbon black composites, there has been less emphasis on reinforcement mechanisms due to the challenges associated with unraveling the intermolecular interactions. In this paper, a coarse grained molecular dynamics simulation was employed to examine the relationship between the morphology of the carbon black particles and the mechanical properties of the elastomer nanocomposites. Specifically, three different morphological carbon black nanoparticle models, including the smooth particle model, rough particle model, and the rough ellipsoid model, were constructed first. We then focused on investigating the changes of the mechanical properties by systematically varying the filling fraction of the carbon black particles, and the strength of the interfacial interaction between the filler and the rubber. The results indicated that the surface roughness and the filler's shape had a significant impact on the mechanical properties of the filled rubber models. The mechanical enhancement effect of the rough ellipsoidal carbon black is around 50-400% higher than that of the smooth carbon black, and the stronger the interfacial interactions, the more pronounced the enhancement. In addition, the rough ellipsoid filled system has low hysteresis, low permanent deformation, and high fatigue resistance. In general, this work explores the strengthening mechanism of carbon black on the elastomer at the molecular level and generates new insight into the design and fabrication of novel reinforcing fillers.

Contribution of ADD3 and the HLA Genes to Biliary Atresia Risk in Chinese.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10-11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10-4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

"Green transit-oriented development": Exploring the association between TOD and visible green space provision using street view data.

Environmental inequalities generated by transit-oriented development (TOD) are of planning and policy relevance in developing countries. Existing literature has pointed out that TOD has the effect of 'place making', which means the newly developed transit systems may be able to change the environment and amenities of a certain area. While previous studies have largely focused on environment hazards such as noise and pollution induced by transit systems, scant attention has been paid to visible green space provision at station areas. This study develops a new and systematic framework to assess potential disparities in quality and quantity aspects of visible green space provision around subway stations. We explore the effects of TOD on visible green space provision around subway stations using spatial regression models. The results show that there are disparities in visible green space provision around subway stations, but such disparities tend to fade with distance away from stations. We also find that population density, land use mix, intersection density and bus stop density are significantly associated with quantity and quality aspects of visible green space provision around subway stations.

Efficacy and safety of primary customized phacoemulsification combined with goniosynechialysis for refractory acute primary angle closure.

PURPOSE: To assess the safety, efficacy, and long-term clinical outcomes of primary customized phacoemulsification (phaco) combined with goniosynechialysis (GSL; phaco-GSL) in refractory acute primary angle closure (APAC) eyes with uncontrolled high intraocular pressure (IOP). METHODS: This retrospective case series comprised 51 eyes of 42 consecutive patients with refractory APAC and high IOP who were treated using primary customized phaco-GSL at 3 hospitals in China, from 2014 to 2021. Preoperative and postoperative IOP, corrected distant visual acuity (CDVA), corneal endothelial cell density (CECD), intraoperative and postoperative complications were recorded. The safety, efficacy and subsequent long-term clinical outcomes were analyzed. RESULTS: The mean CDVA (LogMAR) was improved from 1.67 ± 0.94 preoperatively to 0.23 ± 0.26 postoperatively (P < 0.001). Preoperative CECD was 2309.39 ± 541.03 cells/mm2 in 33 eyes and inaccessible in 18 eyes due to severe corneal edema; at the final follow-up, the mean CECD of all patients was 1823.50 ± 533.40 cells/mm2 (P < 0.001). The mean IOP decreased from 48.51 ± 6.25 mmHg preoperatively to 15.66 ± 2.27 mmHg at the final follow-up (P < 0.001). Among 51 eyes, additional customized procedures performed were corneal indentation in 42 eyes, epithelial debridement in 9 eyes, giant epithelial bullae view in 4 eyes, pars-plana fluid aspiration in 3 eyes, and secondary intraocular lens implantation in 7 eyes. The IOP of all eyes was well controlled eventually and 47 eyes (92.16%) were successfully treated by phaco-GSL alone. No significant intraoperative or postoperative complications were observed. CONCLUSIONS: Primary customized phaco-GSL is a safe and effective surgical management strategy for patients with refractory APAC and high IOP.

Postoperative intraocular lens stability following cataract surgery with or without primary posterior continuous curvilinear capsulorrhexis: an intra-individual randomized controlled trial.

PURPOSE: To evaluate the effect of primary posterior continuous curvilinear capsulorrhexis (PPCCC) on the positional stability of IOLs. METHODS: This study is a prospective intra-individual comparative randomized controlled trial including 31 patients (62 eyes). Eyes of the same patient were randomly assigned to the PPCCC group (18 right eyes and 13 left eyes) or group without PPCCC (NPCCC group). Eyes in both groups were implanted with a one-piece foldable hydrophobic acrylic IOL via routine cataract surgery. Patients in the PPCCC group underwent additional manual PPCCC before IOL implantation. Examinations were performed 1 day, 1 week, 1 month and 3 months postoperatively. IOL tilt (x, y), decentration (x, y), anterior chamber depth (z) and refractive prediction error data were collected and analyzed with Pentacam. RESULTS: Postoperatively, the range of IOL position change over 3 months in PPCCC group was comparable to NPCCC group, which indicated smaller value in every tilt and decentration index. PPCCC eyes showed comparable tilt and decentration with NPCCC eyes in this study endpoint: mean tilt (x, y), decentration (x, y) and anterior chamber depth (ACD) were 1.04 ± 0.56°, 0.90 ± 0.64°, 0.239 ± 0.140 mm, 0.233 ± 0.133 mm and 4.01 ± 0.32 mm, respectively, in the PPCCC group vs. 1.09 ± 0.76°, 1.10 ± 0.82°, 0.252 ± 0.153 mm, 0.244 ± 0.155 mm and 4.01 ± 0.38 mm, respectively, in the NPCCC group. Refractive prediction error in the PPCCC group demonstrated a mild hyperopic shift vs. the NPCCC group (0.13 ± 0.50 vs. 0.05 ± 0.39; p = 0.208), and corrected distance visual acuity (CDVA) did not differ between the two groups (0.027 ± 0.014 vs. 0.059 ± 0.185; p = 0.377). CONCLUSIONS: Comparable IOL tilt, decentration, ACD and refractive prediction error were observed in PPCCC eyes with that underwent routine cataract surgery. Little IOL position fluctuation and good visual acuity were shown in PPCCC group over time. TRAIL REGISTRATION: The study was registered at the Chinese Clinical Trial Register Center on May 27th, 2020 (protocol code ChiCTR2000033304, 27/05/2020).

Highly Stable and Selective Sensing of Hydrogen Sulfide in Living Mouse Brain with NiN4 Single-Atom Catalyst-Based Galvanic Redox Potentiometry.

Hydrogen sulfide (H2S) is recognized as a gasotransmitter and multifunctional signaling molecule in the central nervous system. Despite its essential neurofunctions, the chemical dynamics of H2S during physiological and pathological processes remains poorly understood, emphasizing the significance of H2S sensor development. However, the broadly utilized electrochemical H2S sensors suffer from low stability and sensitivity loss in vivo due to sulfur poisoning-caused electrode passivation. Herein, we report a high-performance H2S sensor that combines single-atom catalyst strategy and galvanic redox potentiometry to overcome the issue. Atomically dispersed NiN4 active sites on the sensing interface promote electrochemical H2S oxidation at an extremely low potential to drive spontaneous bipolarization of a single carbon fiber. Bias-free potentiometric sensing at open-circuit condition minimizes sulfur accumulation on the electrode surface, thus significantly enhancing the stability and sensitivity. The resulting sensor displays high selectivity to H2S against physiological interferents and enables real-time accurate quantification of H2S-releasing behavior in the living mouse brain.

Nuplazid suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting PAK4.

BACKGROUND: Due to the high recurrence and low 5-year survival rates of esophageal squamous cell carcinoma (ESCC) after treatment, the discovery of novel drugs for recurrence chemoprevention is of particular importance. METHODS: We screened the FDA-approved drug library and found that Nuplazid, an atypical antipsychotic that acts as an effective 5-HT 2 A receptor inverse agonist, could potentially exert anticancer effects in vitro and in vivo on ESCC. RESULTS: Pull-down results indicated that Nuplazid binds with p21-activated kinase 4 (PAK4), and a kinase assay showed that Nuplazid strongly suppressed PAK4 kinase activity. Moreover, Nuplazid exhibited inhibitory effects on ESCC in vivo. CONCLUSIONS: Our findings indicate that Nuplazid can suppress ESCC progression through targeting PAK4.