Ammonium nitrogen and phosphorus removal by bacterial-algal symbiotic dynamic sponge bioremediation system in micropolluted water: Operational mechanism and transformation pathways.

Construct a bacteria-algae symbiotic dynamic sponge bioremediation system to simultaneously remove multiple pollutants under micro-pollution conditions. The average removal efficiencies of NH4+-N, PO43--P, total nitrogen (TN), and Ca2+ were 98.35, 78.74, 95.64, and 84.92 %, respectively. Comparative studies with Auxenochlorella sp. sponge and bacterial sponge bioremediation system confirmed that NH4+-N and TN were mainly removed by bacterial heterotrophic nitrification - aerobic denitrification (HN-AD). PO43--P was removed by algal assimilation and the generation of Ca3(PO4)2 and Ca5(PO4)3OH, and Ca2+ was removed by algal electron transfer formation of precipitates and microbially induced calcium precipitation (MICP) by bacteria. Algae provided an aerobic environment for the bacterial HN-AD process through photosynthesis, while respiration produced CO2 and adsorbed Ca2+ to promote the formation of calcium precipitates. Immobilization of Ca2+ with microalgae via bacterial MICP helped to lift microalgal photoinhibition. The bioremediation system provides theoretical support for research on micropolluted water treatment while increasing phosphorus recovery pathways.

Loofah sponge crosslinked polyethyleneimine loaded with biochar biofilm reactor for ecological remediation of oligotrophic water: Mechanism, performance, and functional characterization.

The removal of complex pollutants from oligotrophic water is an important challenge for researchers. In this study, the HCl-modified loofah sponge crosslinked polyethyleneimine loaded with biochar (LS/PEI@biochar) biofilm reactor was adapted to achieve efficient removal of complex pollutants in oligotrophic water. On the 35 d, the average removal efficiency of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), calcium (Ca2+), and phosphate (PO43--P) in water was 51, 95, 81, and 77 %, respectively. Additionally, it effectively used a low molecular weight carbon source. Scanning electron microscopy (SEM) results showed that the LS/PEI@biochar biocarrier had superior biofilm suspension performance. Meanwhile, analysis of the biocrystals confirmed Ca2+ and PO43- removal through the generation of CaCO3 (calcite and vaterite) and Ca5(PO4)3OH. This study demonstrated that the system has great efficiency and application prospect in treating oligotrophic water on the laboratory scale, and will be further validated for practical application on large-scale oligotrophic water.

Mechanisms of ammonia, calcium and heavy metal removal from nutrient-poor water by Acinetobacter calcoaceticus strain HM12.

An Acinetobacter calcoaceticus strain HM12 capable of heterotrophic nitrification-aerobic denitrification (HN-AD) under nutrient-poor conditions was isolated, with an ammonia nitrogen (NH4+-N) removal efficiency of 98.53%. It can also remove heavy metals by microbial induced calcium precipitation (MICP) with a Ca2+ removal efficiency of 75.91%. Optimal conditions for HN-AD and mineralization of the strain were determined by kinetic analysis (pH = 7, C/N = 2.0, Ca2+ = 70.0 mg L-1, NH4+-N = 5.0 mg L-1). Growth curves and nitrogen balance elucidated nitrogen degradation pathways capable of converting NH4+-N to gaseous nitrogen. The analysis of the bioprecipitation showed that Zn2+ and Cd2+ were removed by the MICP process through co-precipitation and adsorption (maximum removal efficiencies of 93.39% and 80.70%, respectively), mainly ZnCO3, CdCO3, ZnHPO4, Zn3(PO4)2 and Cd3(PO4)2. Strain HM12 produces humic and fulvic acids to counteract the toxicity of pollutants, as well as aromatic proteins to increase extracellular polymers (EPS) and promote the biomineralization process. This study provides a experimental evidence for the simultaneous removal of multiple pollutants from nutrient-poor waters.

Verteporfin Suppresses YAP-Induced Glycolysis in Breast Cancer Cells.

OBJECTIVE: The inhibition of the Hippo pathway through targeting the Yes-associated protein (YAP) presents a novel and promising approach for treating tumors. However, the efficacy of YAP inhibitors in the context of breast cancer (BC) remains incompletely understood. Here, we aimed to investigate the involvement of YAP in BC's metabolic reprogramming and reveal the potential underlying mechanisms. To this end, we assessed the function of verteporfin (VP), a YAP-TEAD complex inhibitor, on the glycolytic activity of BC cells. METHODS: We evaluated the expression of YAP by utilizing immunohistochemistry (IHC) in BC patients who have undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) prior to biopsy/surgery. We employed RNA immunoprecipitation (RIP) and fluorescent in situ hybridization (FISH) assays to assess the interaction between YAP mRNA and human antigen R (HuR) in BC cells. The biological importance of YAP in the metabolism and malignancy of BC was evaluated in vitro. Finally, the effect of VP on glycolysis was determined by using 18F-FDG uptake, glucose consumption, and lactate production assays. RESULTS: Our studies revealed that high expression of YAP was positively correlated with the maximum uptake value (SUVmax) determined by 18F-FDG PET/CT imaging in BC samples. Inhibition of YAP activity suppressed glycolysis in BC. The mechanism underlying this phenomenon could be the binding of YAP to HuR, which promotes glycolysis in BC cells. Treatment with VP effectively suppressed glycolysis induced by YAP overexpression in BC cells. CONCLUSION: VP exhibited anti-glycolytic effect on BC cells, indicating its therapeutic value as an FDA-approved drug.

Construction of a Programmable Feedback Network with Continuously Activatable Molecular Beacon Fluorescence for One-Step Quantification of Long Noncoding RNAs in Clinical Breast Tissues.

Long noncoding RNAs (lncRNAs) are key regulators in numerous pathological and physiological processes, and their aberrant expression is implicated in many diseases. Herein, we develop a programmable feedback network with continuously activatable molecular beacon (MB) fluorescence for one-step quantification of mammalian-metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) in clinical breast tissues. We introduce a functional MB with three domains, including a substrate for lncRNA MALAT1 recognition, a template for strand displacement amplification (SDA), and a reporter for signal output with FAM fluorescence being quenched by BHQ1. When MALAT1 is present, it recognizes and unfolds the MB, leading to the recovery of FAM fluorescence. Once the MB is opened, multiple rounds of SDA reaction are automatically initiated by recruiting primer, KF DNA polymerase, and Nt.BbvCI nicking enzyme, inducing the opening of more MBs and the dissociation of more FAM/BHQ1 pairs. Consequently, a feedback network is constructed through multicycle cascade SDA, achieving the exponential accumulation of fluorescence signals for accurate quantification of MALAT1. In this assay, only two oligonucleotides (i.e., MB and primer) are involved for the establishment of a feedback amplification network, greatly simplifying the design of the reaction system. Moreover, this assay requires only one step to realize the isothermal exponential amplification for real-time monitoring of MALAT1 with attomolar sensitivity. This assay displays single-base mismatch selectivity with high anti-interference capability, and it can further quantify endogenous MALAT1 at the single-cell level and differentiate MALAT1 expression between breast cancer patient tissues and healthy person tissues.

CircANKRD17 promotes glycolysis by inhibiting miR-143 in breast cancer cells.

Glucose metabolic reprogramming, known as the Warburg effect, is one of the metabolic hallmarks of tumor cells. Cancer cells preferentially metabolize glucose by glycolysis rather than mitochondrial oxidative phosphorylation regardless of oxygen availability, but the regulatory mechanism underlying this switch has been incompletely understood. Here, we report that the circular RNA circ ankyrin repeat domain 17 (ANKRD17) functions as a key regulator for glycolysis to promote cell growth, migration, invasion, and cell-cycle progression in breast cancer (BC) cells. We further show that circANKRD17 acts to accelerate glycolysis in BC cells by acting as a sponge for miR-143 and in turn overrides the repressive effect of miR-143, a well-documented glycolytic repressor, on hexokinase 2 in BC cells, thus resulting in enhanced glycolysis in BC cells. These data suggest the circANKRD17-miR-143 cascade as a novel mechanism in controlling glucose metabolic reprogramming in BC cells and suggest circANKRD17 as a promising therapeutic target to interrupt cancerous glycolysis.

Label-free and sensitive detection of N6-methyladenosine demethylase activity in crude cell extracts and clinical cancer tissues based on demethylation-triggered exponential signal amplification.

The m6A demethylase catalyzes the removal of m6A modification to establish proper RNA methylation patterns, and it has emerged as a promising disease biomarker and a therapeutic target. The reported m6A demethylase assays often suffer from tedious producers, expensive reagents, radioactive risk, limited sensitivity, and poor specificity. Herein, we develop a simple, selective, label-free, and highly sensitive fluorescent biosensor for m6A demethylase assay based on demethylation-triggered exponential signal amplification. In this biosensor, m6A demethylase-catalyzed demethylation can protect the circular DNA from the digestion by DpnI, subsequently triggering hyperbranched rolling circle amplification to achieve exponential signal amplification for producing abundant ssDNA and dsDNA products. The amplified DNA signal can be sensitively and simply detected by SYBR Gold in a label-free manner. This biosensor avoids any antibodies, washing/separation procedures, and fluorophore-/quencher-labeled probes, great simplifying the assay procedures and reducing the assay cost. Moreover, this biosensor achieves good specificity and excellent sensitivity with a detection limit of 1.2 fg/µL, which is superior to conventional ELISA (36.3 pg/µL). Especially, this biosensor enables direct monitoring of m6A demethylase activity in crude cell extracts with high accuracy, and it can be further applied for the screening of m6A demethylase inhibitor, measurement of m6A demethylase activity in different cell lines, and discrimination of m6A demethylase level in clinical cancer and healthy tissues, providing a facile and robust platform for RNA methylation-related biomedical research, disease diagnosis, and drug discovery.

Construction of Multiple DNAzymes Driven by Single Base Elongation and Ligation for Single-Molecule Monitoring of FTO in Cancer Tissues.

Fat mass and obesity-associated proteins (FTO) play an essential role in the reversible regulation of N6-methyladenosine (m6A) epigenetic modification, and the overexpression of FTO is closely associated with the occurrence of diverse human diseases (e.g., obesity and cancers). Herein, we demonstrate the construction of multiple DNAzymes driven by single base elongation and ligation for the single-molecule monitoring of FTO in cancer tissues. When target FTO is present, the m6A-RNA is specifically demethylated and subsequently acts as a primer to combine with the padlock probe, initiating single-base elongation and ligation reaction to generate a closed template probe. Upon the addition of phi29 DNA polymerase, a rolling circle amplification (RCA) reaction is initiated to produce large numbers of Mg2+-dependent DNAzyme repeats. Subsequently, the DNAzymes cyclically digest the signal probes, liberating numerous Cy5 molecules that can be precisely counted by single-molecule imaging. Taking advantage of the sequence specificity of the polymerase/ligase-mediated gap-filling and ligation as well as the high amplification efficiency of RCA, this biosensor shows excellent specificity and high sensitivity with a detection limit of 5.96 × 10-16 M. It can be applied to screen FTO inhibitors and quantify FTO activity at the single-cell level. Moreover, the proposed strategy can accurately distinguish the FTO expression level in tissues of healthy individuals and breast cancer patients, providing a new platform for drug discovery, m6A modification-related research, and clinical diagnostics.

A novel microRNA-182/Interleukin-8 regulatory axis controls osteolytic bone metastasis of lung cancer.

Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non-small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis.

Simultaneous removal of phosphate, calcium, and ammonia nitrogen in a hydrogel immobilized reactor with bentonite/lanthanum/PVA based on microbial induced calcium precipitation.

In recent years, it is urgent to solve nitrogen and phosphorus pollution in domestic wastewater. The target strain Pseudomonas sp. Y1 was immobilized using polyvinyl alcohol (PVA) matrix coupled with bentonite and lanthanum (La), respectively, to fabricate four hydrogel materials that used to construct bioreactors. The optimal operating parameters and dephosphorization mechanism were discussed, and the effects of hydrogel materials and different loads on the performance of the bioreactor were contrastively analyzed. The results manifested that when the hydraulic retention time (HRT) was 6.0 h, the C/N was 6.0, and the Ca2+ concentration was 100.0 mg L-1, the bioreactors had the best heterotrophic nitrification-aerobic denitrification (HNAD) and biomineralization capacity, and the maximum removal efficiencies of Ca2+, PO43--P, and NH4+-N were 82.57, 99.17, and 89.08%, respectively. The operation data indicated that the addition of bentonite significantly promoted HNAD, and the bioreactor had stronger dephosphorization ability in the presence of La. The main phosphorous removal mechanisms were confirmed to be adsorption and co-precipitation. Finally, high-throughput sequencing results indicated that Pseudomonas accounted for the paramount proportion in the bioreactor, and the prediction of functional genes indicated that the C/N of 6.0 is more favorable for the expression of nitrogen removal-related functional genes in the bioreactor system. This study highlights the superiority of microbial induced calcium precipitation (MICP) combined with PVA hydrogel, and provides a theoretical basis for simultaneous nitrogen and phosphate removal of wastewater.

Venous and Arterial Thromboembolism in Patients with Metastatic Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide with an increasing incidence in many countries. There were few studies on arterial and venous thromboembolism (ATE/VTE) in patients with metastatic lung cancer. Our study focused on the clinical characteristics of stage IV lung cancer patients with ATE or VTE to further explore the risk factors and prognosis. Patients diagnosed with metastatic lung cancer were enrolled from January 2011 to June 2019 at a tertiary hospital in Jiangyin, China. Log-rank test was used to reveal the survival for patients with ATE or VTE. Univariable analysis and multivariable logistic regression were used to study the risk factors for ATE. A total of 587 patients were enrolled in our study, including 52 patients with VTE and 48 with ATE. ATE occurred earlier than VTE. Patients with ATE had a worse prognosis. Multivariable logistic regression revealed that older age and a history of hypertension were independent risk factors for ATE. Patients with metastatic lung cancer were at high risk of VTE and ATE. ATE occurred earlier and was associated with a worse prognosis. Attention should be paid to metastatic lung cancer patients who may develop thromboembolism, especially ATE.

Microencapsulated reactor for simultaneous removal of calcium, fluoride and phenol using microbially induced calcium precipitation: Mechanism and functional characterization.

Fluoride ions (F-) and phenol in groundwater have become a great hurdle to the pursuit of a healthy drinking water source. This study established a microencapsulated immobilization reactor with Aquabacterium sp. CZ3 for the simultaneous removal of nitrate (NO3--N), calcium (Ca2+), F-, and phenol from groundwater with 100%, 67.84%, 88.67%, and 100% removal efficiencies, respectively. The three-dimensional mesh structure of microcapsules facilitated the transport and metabolism of substances, while their synergistic effect with bacteria promoted the removal of contaminants. F- was removed by co-precipitation to generate Ca5(PO4)3F and CaF2 and adsorption. On one hand, the phenol toxicity promoted the production of extracellular polymers and improved the tolerance of bacteria; on the other hand, the degradation of phenol provided a carbon source for bacteria and promoted the denitrification. The development of microencapsulated immobilized reactor provided a clear mechanism for phenol and F- removal under the microbially induced calcium precipitation (MICP) technique, while providing a valuable solution for the treatment of complex groundwater resources.

Enhanced nitrate, fluoride, and phenol removal using polyurethane sponges loaded with rice husk biochar in immobilized bioreactor.

Polyurethane sponges loaded with rice husk biochar were prepared to immobilize Aquabacterium sp. CZ3 for intensified removal of nitrate, fluoride (F-), and phenol, with the maximum efficiency of 100 %, 91 %, and 99 %, respectively. The biochar load and increased carbon-to-nitrogen (C:N) ratio (below 3.0) stimulated the secretion of soluble microbial product, improved the electron transport system activity, and promoted denitrification, phenol co-metabolism, and F- and calcium crystallization. The characterization results suggested that F- was removed as fluoride-containing calcium precipitates. According to the microbial community analyses, Aquabacterium was the dominant bacterium. PICRUSt analyses showed that biochar and adequate carbon sources (C:N ratio 3.0) significantly increased the functional abundances of amino acid metabolism, carbohydrate metabolism, energy metabolism, and cell motility. The introduction of biochar reduces the demand for C:N ratio in the system, and expands the application potential of biomineralization technique in the remediation of multiple pollutants contaminated water.

Synchronous removal of ammonia nitrogen, phosphate, and calcium by heterotrophic nitrifying strain Pseudomonas sp. Y1 based on microbial induced calcium precipitation.

Pseudomonas sp. Y1, a strain with superior synchronous removal ability of ammonia nitrogen (NH4+-N), phosphate (PO43--P), and calcium (Ca2+) was isolated, with the removal efficiencies of 92.04, 99.98, and 83.40 %, respectively. Meanwhile, the chemical oxygen demand (COD) was degraded by 90.33 %. Through kinetic analysis, the optimal cultivated conditions for heterotrophic nitrification-aerobic denitrification (HNAD) and biomineralization were determined. The growth curves experimental results of different nitrogen sources indicated that strain Y1 could remove NH4+-N through HNAD. The results of excitation-emission matrix (EEM) proved that the appearance of extracellular polymeric substances (EPS) promoted the precipitation of phosphate minerals. Finally, the characterization results of the bioprecipitates showed that the HNAD process produced the alkalinity required for microbial induced calcium precipitation (MICP), resulting in the removal of PO43- via adsorption and co-precipitation. This study provides a theoretical basis for the application of microorganisms to achieve synchronous nutrient removal and phosphorus recovery in wastewater.

Chitosan and carboxymethyl chitosan mimic biomineralization and promote microbially induced calcium precipitation.

This research aimed to evaluate chitosan (CTS) and carboxymethyl chitosan (CMCS) as polysaccharides that could mimic the role of bacterial extracellular polymeric substance (EPS) in the biomineralization process through bionic experiments. The introduction of COOH resulted in higher calcium precipitation efficiency of CMCS (65.07%) than CTS (55.66%). CaCO3 nucleation on the surface of CTS and CMCS was triggered through the binding of Ca2+ to NH2, OH, COOH and NHCOCH3 groups. Moreover, the experiment of polysaccharides mediated biomineralization was conducted. The maximum calcium precipitation efficiency reached 96.07% with the addition of 0.15% CMCS. Combining the characterization results, the synergetic mineralization mechanisms between polysaccharides and bacteria were proposed. Among them, bacterial metabolic by-products (alkalinity), active groups and adhesion of polysaccharides played a significant role. This work provides a reference for further understanding of the biomineralization mechanism, and gives a new insight into the intensified strategies of MICP technology.

Microbial induced calcium precipitation based anaerobic immobilized biofilm reactor for fluoride, calcium, and nitrate removal from groundwater.

In this study, the anaerobic quartz sand fixed biofilm reactor containing Cupriavidus sp. W12 was established to simultaneously remove calcium (Ca2+), fluoride (F-) and nitrate (NO3-N) from groundwater. After 84 days of continuous operation, the optimum operating parameters and defluoridation mechanism were explored, and the microbial community structure under different pH environments were compared and analyzed. Under the optimal operation conditions (HRT of 6 h, initial Ca2+ concentration of 180 mg L-1, and pH of 7.0), the removal efficiencies of Ca2+, F-, and NO3-N were 58.97%, 91.93%, and 100%, respectively. Gas chromatography (GC) results indicate that N2 is the main gas produced by the bioreactor. Three-dimension excitation emission matrix fluorescence spectroscopy (3D-EEM) showed that extracellular polymers (EPS) are produced during bacterial growth and metabolism. The results of Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), and Fourier transform infrared spectrometer (FTIR) demonstrated that the defluoridation mechanism is attributed to the synergetic effects of ion exchange, co-precipitation, and chemisorption. The comparative analysis of the microbial community structure under different pH conditions show that Cupriavidus is the dominant bacteria in the bioreactor throughout the experiment, and it shows a prominent advantage at pH of 7.0. This research provides an application foundation for anaerobic microbial induced calcium precipitation (MICP) bioremediation of Ca2+, F-, and NO3-N from groundwater.

Two MicroRNAs, miR-34a and miR-125a, Are Implicated in Bicuspid Aortopathy by Modulating Metalloproteinase 2.

It has been recognized that wall shear stress plays an important role in the development of Bicuspid Aortopathy (BA), but the intrinsic mechanism is not well elucidated. This study aims to explore the underlying relationship between hemodynamical forces and pathological phenomenon. Total RNA was prepared from aortic wall tissues collected from 20 BA patients. RNA sequencing, bioinformatic analysis and quantitative reverse-transcription PCR validation identified nine miRNAs that were up-regulated in the aortic part exposed to high wall shear stress compared to the low wall shear stress control, and six miRNAs that were down-regulated. Among these candidates, miR-34a and miR-125a, both down-regulated in the high wall shear stress parts, were shown to be potential inhibitors of the metalloproteinase 2 gene. Luciferase reporter assays confirmed that both miRNAs could inhibit the expression of metalloproteinase 2 mRNA in CRL1999 by complementing with its 3' untranslated region. Conversely, immunofluorescence assays showed that inhibition of miR-34a or miR-125a could lead to increased metalloproteinase 2 protein level. On the other hand, both miR-34a and miR-125a were shown to alleviate stretch-induced stimulation of metalloproteinase 2 expression in CRL1999 cells. The results suggested that miR-34a and miR-125a might be implicated in wall shear stress induced aortic pathogenesis due to their apparent regulatory roles in metalloproteinase 2 expression and extracellular matrix remodeling, which are key events in the weakening of aortic walls among BA patients.

Prohibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility.

Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.

PHB regulates meiotic recombination via JAK2-mediated histone modifications in spermatogenesis.

Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been investigated. Here we document the presence of PHB in spermatocytes and its functional roles in meiosis by generating the first male germ cell-specific Phb-cKO mouse. Loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest with accompanying apoptosis, but also apoptosis resulting from mitochondrial morphology and function impairment. Our mechanistic studies show that PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway, and consequently promotes meiotic DSB repair and homologous recombination. Furthermore, the PHB/JAK2 axis was found as a novel mechanism in the maintenance of stabilization of meiotic STAG3 cohesin complex and the modulation of heterochromatin formation in spermatocytes during meiosis. The observed JAK2-mediated epigenetic changes in histone modifications, reflected in a reduction of histone 3 tyrosine 41 phosphorylation (H3Y41ph) and a retention of H3K9me3 at the Stag3 locus, could be responsible for Stag3 dysregulation in spermatocytes with the loss of PHB.

Housing affordability effects on physical and mental health: household survey in a population with the world's greatest housing affordability stress.

BACKGROUND: We examined the association of housing affordability with physical and mental health in Hong Kong, where there is a lack of related research despite having the worst housing affordability problem in the world, considering potential mediating effect of deprivation. METHODS: A stratified random sample of 1978 Hong Kong adults were surveyed. Housing affordability was defined using the residual-income (after housing costs) approach. Health-related quality of life was assessed by the Short-Form Health Survey version 2 (SF-12v2), from which the physical component summary (PCS) and mental component summary (MCS) measures were derived. Multivariable linear regressions were performed to assess associations of housing affordability with PCS and MCS scores, adjusting for sociodemographic, socioeconomic and lifestyle factors. Mediation analyses were also conducted to assess the mediating role of deprivation on the effect of housing affordability on PCS or MCS. RESULTS: Dose-response relationships were observed between housing affordability and mean PCS score (ß (95% CI) compared with the highest affordable fourth quartile: -2.53 (-4.05 to -1.01), -2.23 (-3.54 to -0.92), -0.64 (-1.80 to 0.51) for the first, second and third quartiles, respectively) and mean MCS score (ß (95% CI): -3.87 (-5.30 to -2.45), -2.35 (-3.59 to -1.11), -1.28 (-2.40 to -0.17) for the first, second and third quartiles, respectively). Deprivation mediated 34.3% of the impact of housing unaffordability on PCS and 15.8% of that on MCS. CONCLUSIONS: Housing affordability affects physical and mental health, partially through deprivation, suggesting that housing policies targeting deprived individuals may help reduce health inequality in addition to targeting the housing affordability problem.