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Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC classified as a molecularly defined RCC in the fifth edition of the WHO. Most gene alterations in patients with SDH-deficient RCC involve the SDHB subunit, with less involvement of the SDHC, SDHA, and SDHD subunits. Four cases of SDHA-deficient RCC have been reported in the literature, of which one case was associated with an NF2 gene mutation. Herein, we report six novel SDHA-deficient RCC cases, including two cases with NF2 gene mutations. In contrast to the typical morphology of SDH-deficient RCC, the six tumors mainly displayed glandular, sheet-like, or papillary growth patterns with prominent nucleoli (Grades 2–3), among which two cases with NF2 mutations had prominent nucleoli (Grade 3), large transparent vacuoles in the cytoplasm, and a large number of lymphocytes in the stroma. Six tumors showed negative immunohistochemical staining for SDHA and SDHB, and three cases presented with high expression of PD-L1. Second-generation sequencing revealed novel pathogenic somatic SDHA gene mutation and NF2 gene mutations in six and two tumors, respectively. Follow-up data were collected for the six patients with a follow-up time ranging from 7 to 268 months, and all six patients have survived to date. One patient received targeted therapy for tumor metastasis to the lungs after seven months, and another patient with an NF2 gene mutation received immunotherapy for lymph node metastasis revealed during surgery. SDHA-deficient RCCs with NF2 gene mutations have the ability to metastasize but might respond well to immunotherapy. For the first time, we report the largest number of SDHA-deficient RCC cases and comprehensively investigate their clinicopathological and molecular features to provide important guidance for diagnosis and clinical immunotherapy. • SDHA-deficient RCCs displayed solid sheet, glandular or papillary growth distinct from typical SDH RCC. • SDHA-deficient RCCs with NF2 gene mutation presented pleomorphic nuclei, large vacuoles and high PD-L1 expression. • SDHA-deficient RCCs with NF2 gene mutation might exhibit unfavorable prognosis but good immunotherapy effect. [ABSTRACT FROM AUTHOR]

The urbanization and industrialization of cities around the coastal region of the Bohai Sea have produced large amounts of sewage sludge from sewage treatment plants. Research on the biodegradation of nonylphenol (NP) and the influencing factors of such biodegradation during sewage sludge composting is important to control pollution caused by land application of sewage sludge. The present study investigated the effect of aeration on NP biodegradation and the microbe community during aerobic composting under two intermittent aeration treatments in a full-scale plant of sewage sludge, sawdust, and returned compost at a ratio of 6:3:1. The results showed that 65% of NP was biodegraded and that Bacillus was the dominant bacterial species in the mesophilic phase. The amount of NP biodegraded in the mesophilic phase was 68.3%, which accounted for 64.6% of the total amount of biodegraded NP. The amount of NP biodegraded under high-volume aeration was 19.6% higher than that under low-volume aeration. Bacillus was dominant for 60.9% of the composting period under high-volume aeration, compared to 22.7% dominance under low-volume aeration. In the thermophilic phase, high-volume aeration promoted the biodegradation of NP and Bacillus remained the dominant bacterial species. In the cooling and stable phases, the contents of NP underwent insignificant change while different dominant bacteria were observed in the two treatments. NP was mostly biodegraded by Bacillus , and the rate of biodegradation was significantly correlated with the abundance of Bacillus ( r  = 0.63, p  < 0.05). Under aeration, Bacillus remained the dominant bacteria, especially in the thermal phase; this phenomenon possibly increased the biodegradation efficiency of NP. High-volume aeration accelerated the activity and prolonged the survival of Bacillus . The risk of organic pollution could be decreased prior to sewage sludge reuse in soil by adjusting the ventilation strategies of aerobic compost measurements. [ABSTRACT FROM AUTHOR]

Xp11.2 translocation/ TFE3 rearrangement-associated renal cell carcinoma (RCC) and Xp11 translocation renal mesenchymal tumor are distinct tumor entity. To broaden the spectrum of Xp11 neoplasms, we investigated a novel tumor exhibiting morphologies overlapping Xp11.2 translocation/ TFE3 rearrangement-associated RCC and the mesenchymal counterpart with melanocytic differentiation by immunohistochemistry, fluorescence in situ hybridization (FISH) and RNA sequencing, as well as literature review. Histologically, the tumor was composed of three different types of tumor cells, including a large proportion of clear cells, small round cells, and a few spindle cells, presenting a relatively clear border in the majority area. The nuclei of all tumor cells showed extensively and strong positive expressions of TFE3. Whereas, the clear cells positively expressed the RCC-related markers including PAX8, RCC marker and CD10, and negatively expressed HMB45; On the contrary, the small round cells and spindle cells positively expressed melanocytic marker HMB45, and negatively expressed PAX8, RCC marker and CD10. The ki67 index was higher in the small round cells and spindle cells than that in the clear cells. FISH revealed the rearrangement of TFE3 gene in all the three types of cells. The NONO-TFE3 fusion gene was detected in all tumor cells by RNA sequencing. This unique Xp11 translocation-associated neoplasm might represent a distinct entity overlapping Xp11 translocation RCC and the mesenchymal counterpart with melanocytic differentiation, broadening the spectrum of Xp11 neoplasms. The patient died of tumor recurrence and lung metastasis after seven months after the surgery suggesting those tumors have an unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Primary pleomorphic malignant fibrous histiocytoma of the heart is rare. The present study was performed to study the clinical and pathological features of the disease. We describe two rare cases of primary cardiac malignant fibrous histiocytoma and review the published individual data of the patients. Both patients complained of dyspnea, and underwent palliative tumor resection. However, they died several months after surgery. A thorough literature review with clinical presentations, diagnostic features, treatment, and outcomes was done. We have for the first time analyzed the factors related to the survival of malignant fibrous histiocytoma. It is usually difficult to make an appropriate preoperative diagnosis. Despite complete surgical resection and aggressive chemotherapy and radiotherapy, the prognosis is still poor. [Copyright &y& Elsevier]

Abstract Volatile organic compounds (VOCs) are the major components of the odor emitted from sewage sludge composting plants and are generally associated with odorous nuisances and health risks. However, few studies have considered the potential ozone generation caused by VOCs emitted from sewage sludge composting plants. This study investigated the VOC emissions from a full-scale composting plant. Five major treatment units of the composting plant were chosen as the monitoring locations, including the dewatered room, dewatered sludge, blender room, fermentation workshop, and product units. The fermentation workshop units displayed the highest concentration of VOC emissions at 2595.7 ± 1367.3 μg.m−3, followed by the blender room, product, dewatered sludge, and dewatered room units, whose emissions ranged from 142.2 ± 86.8 μg.m−3 to 2107.6 ± 1045.6 μg.m−3. The detected VOC families included oxygenated compounds, alkanes, alkenes, sulfide compounds, halogenated compounds, and aromatic compounds. Oxygenated compounds, particularly acetone, were the most abundant compounds in all samples. Principal component analysis revealed that the dewatered room and dewatered sludge units clustered closely, as indicated by their similar component emissions. The product units differed from the other sampling units, as their typical compounds were methanethiol, styrene, carbon disulfide, and hexane, all of which were the products of the latter stages of composting. Among the treatment units, the fermentation workshop units had the highest propylene equivalent (propy-equiv) concentration. Dimethyl disulfide and limonene were the major contributors. Limonene had the highest propy-equiv concentration, which contributed to the increased atmospheric reactivity and ozone formation potential in the surrounding air. To control the secondary environmental pollution caused by the VOC emissions during sewage sludge composting, the emission of limonene and dimethyl disulfide must be controlled from the blender room and fermentation workshop units. Graphical abstract Unlabelled Image Highlights • VOCs released from different units of a full-scale composting plant were evaluated. • The potential ozone formation of VOCs was analyzed during the summer. • Oxygenated compounds had the highest concentration and acetone was the major species. • Propy-equiv concentration was used to weigh the atmospheric reactivity of the VOCs. • DMDS and limonene were the major contributors to potential ozone formation. [ABSTRACT FROM AUTHOR]

Abstract Composting is a major sludge-treatment method and bulking agents are very important in sludge composting. In this study, ceramsite and activated alumina balls were chosen as recyclable bulking agents for sludge composting. Variations in the temperature, pH, electrical conductivity, organic matter, dissolved organic carbon, moisture content, and heavy metals were detected during composting with different bulking-agent treatments as well as differences in the germination index values. The results showed that both bulking agents could ensure the maturity of the compost; further, ceramsite treatment resulted in the best water removal efficiency. According to the sequential extraction procedure, both ceramsite and activated alumina balls could stabilize Cd but they also increased the mobility of Zn. After comparing the effects of different particle sizes of ceramsite on composting, 20 mm was determined to be the most optimal value. Additionally, the recovery rates of ceramsite and activated alumina balls were 96.9% and 99.9%, respectively. Graphical abstract Image 1 Highlights • Ceramsite and AAB were chosen as recyclable bulking agents for composting. • Ceramsite improved organic matter degradation and water removal during composting. • Both ceramsite and AAB stabilised Cd in sludge by compost treatment. • Optimal particle size of ceramsite for use as a composting bulking agent was 20 mm. • Both ceramsite and AAB had good recycling potential as bulking agents for composting. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Qishen Yiqi is a widely used Chinese herbal medicine formula with “qi invigorating and blood activating” property. Its dripping pill preparation (QSYQ) is a commercial herbal medicine approved by the China Food and Drug Administration (CFDA) in 2003 and is extensively used clinically to treat cardiovascular diseases, such as ischemic heart failure and angina pectoris, as well as for the secondary prevention of myocardial infarction. However, the bioactive ingredients of QSYQ remain unclear. As QSYQ is a compound herbal formula, it is of great importance to elucidate its pharmacologically active ingredients and underlying synergetic effects. Aim of the study This experimental study was conducted to comprehensively determine the combinatorial bioactive ingredients (CBIs) in QSYQ and to elucidate their potential synergetic effects. The established strategy may shed new light on how to rapidly determine CBIs in complex herbal formulas with holistic properties. Materials and methods An integrated evidence-based targeting strategy was introduced and validated to determine CBIs in QSYQ. The strategy included the following steps: (1) Chemical ingredients in QSYQ were analyzed via UPLC-Q-TOF/MS in the negative and positive modes and were identified by comparison with standard compounds and previously reported data. Their potential therapeutic activities were predicted based on the ChEMBL database to preliminarily search for candidate bioactive ingredients, and their combination was defined as the CBIs. (2) The CBIs were directly trapped and prepared from QSYQ with a two-dimensional chromatographic separation system, and the remaining part was defined as the rest ingredients (RIs). (3) As animal and cell models, left anterior descending coronary artery ligation (LAD)-induced heart failure in rats and hypoxia-induced cardiac myocyte injury in H9c2 cells were applied to compare the potency of QSYQ, CBIs and RIs. (4) The synergetic effects on cardiac myocyte protection of multiple ingredients in CBIs were examined in this cell model. Results (1) Forty-three ingredients in QSYQ were identified via UPLC-Q-TOF/MS. Based on evidence-based screening using the ChEMBL database, 24 ingredients were predicted to be bioactive ingredients, and their combination was considered the CBIs. (2) The CBIs and RIs were successfully prepared according to a two-dimensional chromatographic system. The CBIs were directly trapped and knocked out from QSYQ by hydrophilic interaction liquid chromatography coupled with reverse-phase liquid chromatography. The remaining part was used as RIs. (3) The results from pharmacological evaluation revealed that CBIs and QSYQ, but not RIs, significantly prevented myocardium injury; improved the ejection fraction (EF) and fractional shortening (FS); decreased the release of cardiac enzymes, including CK, CK-MB, and LDH; alleviated mitochondrial dysfunction; and protected the cell nucleus number and mitochondrial mass. Furthermore, QSYQ and CBIs possessed similar potency. (4) In hypoxia-stimulated H9c2 cells, CBIs showed far greater potency regarding the protection of cardiac myocyte injury than the individual ingredients in QSYQ, exhibiting obvious synergetic effects. Conclusions An integrated evidence-based targeting strategy was successfully established and validated to determine CBIs from QSYQ with excellent efficiency. Importantly, the holistic property of QSYQ was retained in the CBIs. Hence, this study may shed new light on how to rapidly reveal combinatorial bioactive ingredients from complex prescriptions and will be greatly helpful in the establishment of an appropriate approach to quality control for herbal medicines. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP), the most extensively used phthalate acid esters (PAEs), poses a potential risk to human and environment. A novel bacterial strain, Rhodococcus sp. LW-XY12, with efficient PAE-degrading capability, was isolated from activated sludge. Strain LW-XY12 could degrade 96.91 ± 0.68% of DEHP (500 mg L−1) within 32 h. The degradation curves of DEHP (50–1500 mg L−1) and PAE mixture (500 mg L−1 each) fitted well with the modified Gomperz kinetics model. DEHP metabolic pathway was reconstructed by using genome annotation and metabolic intermediate analyses. The DEHP metabolic pathway might comprise de-esterification and β-oxidation. Homologous modeling and molecular docking analysis revealed that DEHP and MEHP (mono-(2-ethylhexyl) phthalate) could be bound to putative carboxylesterase (KXC42_04905) via hydrogen bonding and hydrophobic interaction. A conserved catalytic triad (Ser195-Glu319-His412) might act as an active protein pocket and catalyze the hydrolysis of DEHP. Carboxylesterase (KXC42_04905) could hydrolyze ester bond and a possible mechanism underlying ester bond hydrolysis catalyzed by the carboxylesterase was proposed. Protocatechuate 3,4-dioxygenase, 3-oxoadipate CoA-transferase, benzoate 1,2-dioxygenase, catechol 1,2-dioxygenase, and catechol 2,3-dioxygenase transcripts were detected and significantly up-regulated under DEHP induction. This study sheds light on the functional genes associated with DEHP degradation and metabolic mechanism in this versatile bacterium for degradation of PAEs. [Display omitted] • Strain Rhodococcus sp. LW-XY12 degraded DEHP and other PAE homologs efficiently. • DEHP and PAE mixture degradation curves fitted well with the modified Gompertz model. • Interactions between a carboxylesterase and DEHP and underlying mechanism were explored. • Strain LW-XY12 may degrade catechol through ortho- and/or meta-cleavage pathways. • DEHP metabolism pathway was reconstructed by metabolite analyses and genomic annotation. [ABSTRACT FROM AUTHOR]

Abstract: Papillary renal cell carcinoma (PRCC) includes two different morphological subtypes. The differences of genetics and ultrastructure of the two subtypes have been rarely reported. Also, new biomarkers related to the diagnosis and prognosis of PRCC have still not been well elucidated. Immunohistochemistry, fluorescence in situ hybridization (FISH) and transmission electron microscopy were used systematically to determine the characteristics of 56 cases of PRCC and to reveal new diagnostic and prognostic information. Type 1 PRCC presented higher expression rates of EMA and CK7, whereas type 2 presented a higher expression rate of CD10. New immunohistochemical markers, including: p504s, PAX-2, PAX-8 and CA-IX showed extensive immunostaining in PRCC. We first revealed a distinct immunostaining pattern of CA-IX, which was located in multiple foci in PRCC. All tumors had at least one chromosomal aberration including loss of Y, gains of 7 or 17. Gain of chromosome 17 was common in type 1; losses of chromosome 18, 11 and 8 appeared in type 2. Ultrastructurally, glycogen granules and secondary lysosomes were seen in type 1, mitochondria and smooth endoplasmic reticulum were scattered in type 2. Tumor subtype, nuclear grade, TNM stage, clear cell renal cell carcinoma (CCRCC) component and sarcomatoid elements, metastasis, CAIX expression, losses of chromosome 18 and 8 were related to poor outcome of PRCC. We conclude that the two subtypes of PRCC originate from different renal cells, and arise from partially common genetic pathways. EMA, CK7, CD10, p504s, PAX-2, PAX-8 and CA-IX are helpful markers in the differential diagnosis of PRCC. CA-IX expression, losses of chromosome 18 and 8 are new prognostic factors of PRCC. [Copyright &y& Elsevier]