A Novel Set-Based Discrete Particle Swarm Optimization for Wastewater Treatment Process Effluent Scheduling.

With the escalating severity of environmental pollution caused by effluent, the wastewater treatment process (WWTP) has gained significant attention. The wastewater treatment efficiency and effluent quality are significantly impacted by effluent scheduling that adjusts the hydraulic retention time. However, the sequential batch and continuous nature of the effluent pose challenges, resulting in complex scheduling models with strong constraints that are difficult to tackle using existing scheduling methods. To optimize maximum completion time and effluent quality simultaneously, this article proposes a restructured set-based discrete particle swarm optimization (RS-DPSO) algorithm to address the WWTP effluent scheduling problem (WWTP-ESP). First, an effective encoding and decoding method is designed to effectively map solutions to feasible schedules using temporal and spatial information. Second, a restructured set-based discrete particle swarm algorithm is introduced to enhance the searching ability in discrete solution space via restructuring the solution set. Third, a constraint handling strategy based on violation degree ranking is designed to reduce the waste of computational resources. Fourth, a Sobel filter based local search is proposed to guide particle search direction to enhance search efficiency ability. The RS-DPSO provides a novel method for solving WWTP-ESP problems with complex discrete solution space. The comparative experiments indicate that the novel designs are effective and the proposed algorithm has superior performance over existing algorithms in solving the WWTP-ESP.

Facet-Dependent Interfacial Charge Transfer between T-Phase VS2 Nanoflakes and Rutile TiO2 Single Crystals.

The hybridizations of two-dimensional (2D) metallic materials with semiconducting transition metal oxides (TMOs) register attractive heterojunctions, which can find various applications in photostimulated circumstances. In this work, we developed an ambient-pressure chemical vapor deposition method to directly grow T-VS2 on atomically smooth rutile TiO2 single crystals with different terminations and thus successfully constructed a heterojunction model of VS2/TiO2 with a well-defined clean interface. Detailed measurements with Kelvin probe force microscopy revealed the facet-dependent charge transfer occurring at the VS2/TiO2 interfaces, seeing variations not only in the amount and direction of the transferred electrons but also in the photoinduced surface potential changes and the dynamics of photogenerated charge carriers under ultraviolet irradiation. Interestingly, ultrathin T-VS2 was found with considerable magnetism at room temperature, disregarding the charge exchange with the TiO2 substrates. These results may bring deep insights into the photoinspired functionalities of the hybridized system combining metallic transition metal dichalcogenides and TMO materials.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Application Effect of Comprehensive Noise Reduction Technology in Outpatients with Vitiligo: A Retrospective Study.

OBJECTIVE: Noise is a kind of perceived public nuisance that is closely related to people's subjective feelings and lives. This study explores the clinical application effect of comprehensive noise reduction technology in outpatients with vitiligo. METHODS: A total of 76 patients with vitiligo were selected in the Department of Dermatology at Baoding No. 2 Central Hospital from January 2020 to January 2021, as the control group (CG), receiving 5S management mode, and 80 patients with vitiligo from February 2021 to October 2022 were selected as the study group (SG), receiving comprehensive noise reduction technology combined with the 5S management mode for this retrospective study. The effects of different management modes on these patients were observed. RESULTS: SG had higher nursing quality scores in service attitude, service initiative, communication skills, environmental management and item management and overtly a lower noise level than CG (all P < 0.001). The Hamilton Anxiety Scale (HAMA) scores of the two groups at the end of treatment were significantly lower than those on admission (P < 0.05), with SG showing a lower score than CG (P < 0.001). Correlation analysis showed that noise levels and HAMA scores had a positive correlation (r = 0.423, P < 0.001). Patients with negative feelings about medical treatment caused by various noise sources in SG were obviously less than those in CG (P < 0.05). Both the groups had a statistical difference in overall satisfaction (P < 0.05). CONCLUSION: The investigation and data analysis demonstrated that comprehensive noise reduction in outpatients with vitiligo had a considerable effect. This technology can standardise the behaviour of medical staff, enhance nursing quality, reduce noise levels and alleviate patients' anxiety and improve their satisfaction. It has great benefits for the outpatient environment and patients.

Genome analysis of a newly isolated Bacillus velezensis-YW01 for biodegrading acetaldehyde.

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL.

Tooth whitening: current status and prospects.

As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects.

Development and validation of a clinical and ultrasound features-based nomogram for preoperative differentiation of renal urothelial carcinoma and central renal cell carcinoma.

PURPOSE: This study aimed to develop and validate an ultrasound (US)-based nomogram for the preoperative differentiation of renal urothelial carcinoma (rUC) from central renal cell carcinoma (c-RCC). METHODS: Clinical data and US images of 655 patients with 655 histologically confirmed malignant renal tumors (521 c-RCCs and 134 rUCs) were collected and divided into training (n = 455) and validation (n = 200) cohorts according to examination dates. Conventional US and contrast-enhanced US (CEUS) tumor features were analyzed to determine those that could discriminate rUC from c-RCC. Least absolute shrinkage and selection operator regression was applied to screen clinical and US features for the differentiation of rUC from c-RCC. Using multivariate logistic regression analysis, a diagnostic model of rUC was constructed and visualized as a nomogram. The diagnostic model's performance was assessed in the training and validation cohorts by calculating the area under the receiver operating characteristic curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness of the US-based nomogram. RESULTS: Seven features of both clinical features and ultrasound imaging were selected to build the diagnostic model. The nomogram achieved favorable discrimination in the training (AUC = 0.996, 95% CI: 0.993-0.999) and validation (AUC = 0.995, 95% CI: 0.974, 1.000) cohorts, and good calibration (Brier scores: 0.019 and 0.016, respectively). DCA demonstrated the clinical usefulness of the US-based nomogram. CONCLUSION: A noninvasive clinical and US-based nomogram combining conventional US and CEUS features possesses good predictive value for differentiating rUC from c-RCC.

Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Barriers and facilitators to using ophthalmic clinical health services following school vision screening: a mixed-methods study.

OBJECTIVE: To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening. METHODS: This study employed a sequential explanatory mixed methods design, underpinned by Andersen's Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders-comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings. RESULTS: The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence. CONCLUSION: The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.

Cadmium aggravates liver injury by activating ferroptosis and neutrophil extracellular traps formation in Nile tilapia (Oreochromis niloticus).

Cadmium (Cd) is a pervasive environmental contaminant and a significant risk factor for liver injury. The present study was undertaken to evaluate the involvement of ferroptosis and neutrophil extracellular traps (NETs) in Cd-induced liver injury in Nile tilapia (Oreochromis niloticus), and to explore its underlying mechanism. Cd-induced liver injury was associated with increased total iron, malondialdehyde (MDA), and Acyl-CoA synthetase long-chain family member 4 (ACSL4), together with reduced levels of glutathione, glutathione peroxidase-4a (Gpx4a), and solute carrier family 7 member 11 (SLC7A11), which are all hallmarks of ferroptosis. Moreover, liver hyperemia, neutrophil infiltration, increased inflammatory factors and myeloperoxidase, as well as elevated serum DNA content in Cd-stimulated Nile tilapia suggested that a considerable number of neutrophils were recruited to the liver. Furtherly, in vitro experiments demonstrated that Cd induced the formation of NETs, and the possible mechanism was related to the generation of reactive oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, along with the P38 and extracellular regulated protein kinase (ERK) signaling pathways. We concluded that ferroptosis and NETs are the critical mechanisms contributing to Cd-induced liver injury in Nile tilapia. These findings will contribute to Cd toxicological studies in aquatic animals.

Exploring the regulatory role of non-coding RNAs in fiber development and direct regulation of GhKCR2 in the fatty acid metabolic pathway in upland cotton.

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation.

Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2" PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when crosslinked with PD-L1+ cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/Treg cells in the tumor microenvironment (TME), rendering an immunologically "cold" tumor "hot". Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA-sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well-tolerated and did not induce hepatotoxicity in non-human primates. According to computational semi-mechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1-rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 crosslinking-dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors.

Mitophagy defect mediates the aging-associated hallmarks in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal disease manifested by premature aging and aging-related phenotypes, making it a disease model for aging. The cellular machinery mediating age-associated phenotypes in HGPS remains largely unknown, resulting in limited therapeutic targets for HGPS. In this study, we showed that mitophagy defects impaired mitochondrial function and contributed to cellular markers associated with aging in mesenchymal stem cells derived from HGPS patients (HGPS-MSCs). Mechanistically, we discovered that mitophagy affected the aging-associated phenotypes of HGPS-MSCs by inhibiting the STING-NF-ĸB pathway and the downstream transcription of senescence-associated secretory phenotypes (SASPs). Furthermore, by utilizing UMI-77, an effective mitophagy inducer, we showed that mitophagy induction alleviated aging-associated phenotypes in HGPS and naturally aged mice. Collectively, our results uncovered that mitophagy defects mediated the aging-associated markers in HGPS, highlighted the function of mitochondrial homeostasis in HGPS progression, and suggested mitophagy as an intervention target for HGPS and aging.

Lactate-driven type I collagen deposition facilitates cancer stem cell-like phenotype of head and neck squamous cell carcinoma.

Lactate is known to play a crucial role in the progression of malignancies. However, its mechanism in regulating the malignant phenotype of head and neck squamous cell carcinoma (HNSCC) remains unclear. This study found that lactate increases cancer stem cell (CSC) characteristics of HNSCC by influencing the deposition of type I collagen (Col I). Lactate promotes Col I deposition through two distinct pathways. One is to convert lactate to pyruvate, a substrate for Col I hydroxylation. The other is the activation of HIF1-α and P4HA1, the latter being a rate-limiting enzyme for Col I synthesis. Inhibition of these two pathways effectively counteracts lactate-induced enhanced cell stemness. Further studies revealed that Col I affects CSC properties by regulating cell cycle dynamics. In conclusion, our research proposes that lactate-driven Col I deposition is essential for the acquisition of CSC properties, and lactate-centric Col I deposition may be an effective target for CSCs.

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

A novel mutation in GTPBP3 causes combined oxidative phosphorylation deficiency 23 by affecting pre-mRNA splicing.

Background: Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) is a rare mitochondrial disease caused by mutations in the GTPBP3 gene. The rare incidence of the disease and the high clinical heterogeneity pose challenges in making a precise diagnosis. Investigations into the rare COXPD23 patients are of pathophysiological and etiological value. In this study, we investigated the genotype-phenotype relationship in a COXPD23 patient from a Manchu family, with GTPBP3 mutations. Methods: Routine physical examinations, laboratory assays and imaging analyses were performed. The metabolic profiles of amino acids in blood, acylcarnitine in blood and organic acids in urine were used to determine the presence of inherited metabolic diseases. Genetic variations in the family were investigated using whole-exome sequencing and Sanger sequencing. Splicing disruption by a mutation was predicted and verified using a minigene assay. Results: The patient presented with severe lactic acidosis, neurological symptoms, multiple symmetrical lesions in the brain and serious mitochondrial energy metabolism disturbances. The c.689A > C (p.Q230P) and c.809-1_809delinsA compound heterozygous mutations were detected in GTPBP3. The novel c.809-1_809delinsA mutation was located at the splicing site of exon 7 and intron 6 and multiple tools predicted that it would disrupt the normal splicing. The minigene assay proved that the novel mutation resulted in two aberrant transcripts that created premature termination codons. Conclusions: The clinical manifestations, brain imaging change, mitochondrial metabolism disturbances and the detection and validation of the GTPBP3 mutations expand the profile of COXPD23 and the pathogenic mutation spectrum. Our study improves the understanding of the pathophysiology and etiology of COXPD23.

Parkin deficiency promotes liver cancer metastasis by TMEFF1 transcription activation via TGF-ß/Smad2/3 pathway.

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.

Enhancement of Broadband Reverse Saturable Absorption of Red/Black Phosphorus Heterojunction.

Although laser technology brings convenience to production and daily life, it also causes high-energy damage. Therefore, there is an urgent need to develop optical limiting materials for laser protection. In this study, a novel nonlinear optical material, red/black phosphorus lateral heterojunction, is successfully prepared through solvothermal and ultrasonic treatment. Using the Z-scan method, the nonlinear optical properties of the red/black phosphorus heterojunction are determined at wavelengths of 532 and 1064 nm. These results indicate that the red/black phosphorus heterojunction exhibits reverse saturable absorption properties in 1.2.3-glycerol. Interestingly, the red/black phosphorus heterojunction shows an enhanced performance over red phosphorus by introducing the black phosphorus phase. Moreover, the red/black phosphorus heterojunction is doped into organically modified silicate gel glass with excellent broadband optical limiting performance. This study highlights the promising prospect of the red/black phosphorus heterojunction in the nonlinear optical and optical limiting fields.