Investigational Treatment of Congenital Hypogonadotropic Hypogonadism in Infants.

The aim of the study was to investigate whether the administration of gonadotropins to mimic the physiological development of infants with congenital hypogonadotropic hypogonadism (CHH) after birth can facilitate testicular descent, penile growth, and ultimately preserve fertility. This study included eight infants with CHH who received a gonadotropin-releasing hormone (GnRH) pump or human chorionic gonadotropin (HCG) combined with human menopausal gonadotropin (HMG) therapy at Beijing Children's Hospital from August 2018 to March 2023. The age of the infants ranged from 6 months to 2 years. 2. For literature review, a search was conducted in the PubMed database using the keywords "congenital hypogonadotropic hypogonadism," "infants," and "mini-puberty" up until June 2023. After 1-3 months of treatment, significant increases were observed in PL and TV. The testes descended from the inguinal region to the scrotum. Serum T and INH-B levels increased from being undetectable to 737.1±409.5 ng/dl and from 47.88±23.03 to 168.94±59.34 pg/ml, respectively. In a comparative literature review of 22 infants with CHH, the age at treatment initiation ranged from 0.5 to 7.9 months. Treatment involved various dosages and durations, ranging from 2 to 6 months of subcutaneous injections of LH and FSH. Both therapies successfully improved PL, TV, and testicular descent; reduced the need for surgery; and were safe. This is the first report of the use of a GnRH pump for the treatment of infant CHH.

Analysis of genetic and clinical characteristics of androgen insensitivity syndrome: a cohort study including 12 families.

CONTEXT: Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46,XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals. METHODS: This was a cohort study that analyzed the genetic and clinical characteristics of patients with AIS from a single center in China. RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit, the median age was 1.83 years (0.92-4.17), and the external masculinization score was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H (n = 5) and p.R841C (n = 2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from 1 case were inherited from his maternal grandfather who had hypospadias. CONCLUSION: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.

The effect of quorum sensing on cadmium- and lead-containing wastewater treatment using activated sludge: Removal efficiency, enzyme activity, and microbial community.

Quorum sensing (QS) is prevalent in activated sludge processes; however, its essential role in the treatment of heavy metal wastewater has rarely been studied. Therefore, in this study, acyl homoserine lactone (AHL)-mediated QS was used to regulate the removal performance, enzyme activity, and microbial community of Cd- and Pb-containing wastewater in a sequencing batch reactor (SBR) over 30 cycles. The results showed that exogenous AHL strengthened the removal of Cd(II) and Pb(II) in their coexistence wastewater during the entire period. The removal of NH4+-N, total phosphorus, and chemical oxygen demand (COD) was also enhanced by the addition of AHL despite the coexistence of Cd(II) and Pb(II). Meanwhile, the protein content of extracellular polymeric substances was elevated and the microbial metabolism and antioxidative response were stimulated by the addition of AHL, which was beneficial for resistance to heavy metal stress and promoted pollutant removal by activated sludge. Microbial sequencing indicated that AHL optimized the microbial community structure, with the abundance of dominant taxa Proteobacteria and Unclassified_f_Enterobacteriaceae increasing by 73.9% and 59.2% maximally, respectively. This study offers valuable insights into the mechanisms underlying Cd(II) and Pb(II) removal as well as microbial community succession under AHL availability in industrial wastewater.

Fate, abundance and ecological risks of microcystins in aquatic environment: The implication of microplastics.

Microcystins are highly toxic cyanotoxins and have been produced worldwide with the global expansion of harmful cyanobacterial blooms (HABs), posing serious threats to human health and ecosystem safety. Yet little knowledge is available on the underlying process occurring in the aquatic environment with microcystins. Microplastics as vectors for pollutants has received growing attention and are widely found co-existing with microcystins. On the one hand, microplastics could react with microcystins by adsorption, altering their environmental behavior and ecological risks. On the other hand, particular attention should be given to microplastics due to their implications on the outbreak of HABs and the generation and release of microcystins. However, limited reviews have been undertaken to link the co-existing microcystins and microplastics in natural water. This study aims to provide a comprehensive understanding on the environmental relevance of microcystins and microplastics and their potential interactions, with particular emphasis on the adsorption, transport, sources, ecotoxicity and environmental transformation of microcystins affected by microplastics. In addition, current knowledge gaps and future research directions on the microcystins and microplastics are presented. Overall, this review will provide novel insights into the ecological risk of microcystins associated with microplastics in real water environment and lay foundation for the effective management of HABs and microplastic pollution.

Identification of the pyroptosis-related gene signature and risk score model for esophageal squamous cell carcinoma.

Advanced esophageal squamous cell carcinoma (ESCC) still has a dismal prognostic outcome. However, the current approaches are unable to evaluate patient survival. Pyroptosis represents a novel programmed cell death type which widely investigated in various disorders and can influence tumor growth, migration, and invasion. Furthermore, few existing studies have used pyroptosis-related genes (PRGs) to construct a model for predicting ESCC survival. Therefore, the present study utilized bioinformatics approaches for analyzing ESCC patient data obtained from the TCGA database to construct the prognostic risk model and applied it to the GSE53625 dataset for validation. There were 12 differentially expressed PRGs in healthy and ESCC tissue samples, among which eight were selected through univariate and LASSO cox regression for constructing the prognostic risk model. According to K-M and ROC curve analyses, our eight-gene model might be useful in predicting ESCC prognostic outcomes. Based on the cell validation analysis, C2, CD14, RTP4, FCER3A, and SLC7A7 were expressed higher in KYSE410 and KYSE510 than in normal cells (HET-1A). Hence, ESCC patient prognostic outcomes can be assessed by our PRGs-based risk model. Further, these PRGs may also serve as therapeutic targets.

Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development.

As significant posttranslational modifications, ubiquitination and deubiquitination, whose balance is modulated by ubiquitin-conjugating enzymes and deubiquitinating enzymes (DUBs), can regulate many biological processes, such as controlling cell cycle progression, signal transduction and transcriptional regulation. Belonging to DUBs, ubiquitin-specific protease 28 (USP28) plays an essential role in turning over ubiquitination and then contributing to the stabilization of quantities of substrates, including several cancer-related proteins. In previous studies, USP28 has been demonstrated to participate in the progression of various cancers. Nevertheless, several reports have recently shown that in addition to promoting cancers, USP28 can also play an oncostatic role in some cancers. In this review, we summarize the correlation between USP28 and tumor behaviors. We initially give a brief introduction of the structure and related biological functions of USP28, and we then introduce some concrete substrates of USP28 and the underlying molecular mechanisms. In addition, the regulation of the actions and expression of USP28 is also discussed. Moreover, we concentrate on the impacts of USP28 on diverse hallmarks of cancer and discuss whether USP28 can accelerate or inhibit tumor progression. Furthermore, clinical relevance, including impacting clinical prognosis, influencing therapy resistance and being the therapy target in some cancers, is depicted systematically. Thus, assistance may be given to future experimental designs by the information provided here, and the potential of targeting USP28 for cancer therapy is emphasized.

Prevalence and association of diabetic nephropathy in newly diagnosed Chinese patients with diabetes in the Hebei province: A single-center case-control study.

Diabetes is a chronic disease and has huge pressure on patients and the medical system, especially for patients with diabetic complications, for example, diabetic nephropathy. Diabetic nephropathy is a diabetic complication associated with damage to the kidney. To improve the quality of life of patients with diabetes, it is necessary to understand the factors that are associated with diabetic nephropathy. The objective of the study was to find the prevalence of diabetic nephropathy in newly diagnosed patients with diabetes and to develop the association between clinicopathological parameters and diabetic nephropathy. In a case-control study, demographics, anthropometric, and clinicopathological parameters of a total of 305 newly diagnosed patients with diabetes (the fasting blood glucose ≥ 7.0 mM/L and/or glycosylated hemoglobin ≥ 6.5 mM/L) in Hebei province were included in the analysis. If the urine albumin to creatinine ratio was ≥ 30 (microalbuminuria) then patients were considered diabetic nephropathy. Among enrolled patients, 206 (68%) were males and 99 (32%) were females and they were 46 to 71 years old. Demographic variables and health-related behaviors were the same among patients with diabetes either with nephropathy (case group, n = 135) or patients without nephropathy (control group, n = 170, P > .05 for all). The prevalence of diabetic nephropathy was 44%. Female to male ratio was 1:1.7 in the case group. Patients with diabetic nephropathy had higher body weight (P < .0001), waist circumference (P = .0006), and body mass index (P = .0002) than those of patients without nephropathy. Abnormal urinary globulin (P = .041, odd ratio (OR): 1.1231) was associated with diabetic nephropathy. Aspartate transaminase (P = .0651, OR: 0.8541), alkaline phosphatase (P = .0661, OR: 0.8122), hypertension (P = .0821, OR: 0.8214), and blood urea nitrogen (P = .0842, OR: 0.9411) were not significantly associated with diabetic neuropathy. However, they are near the statistical cutoff value. The prevalence of diabetic nephropathy in newly diagnosed diabetic patients of Hebei province is higher than those of the other provinces. Urinary globulin excretion had a weak association with the presence of nephropathy defined by urinary albumin excretion in patients with diabetes. The presence of other diabetic complications is also an essential parameter for diabetic nephropathy. Males are more susceptible to diabetic nephropathy than females if diabetic (Evidence Level: V; Technical Efficacy: Stage 3).

Reusable and Practical Biocomposite Based on Sphingopyxis sp. YF1 and Polyacrylonitrile-Based Carbon Fiber for the Efficient Bioremediation of Microcystin-LR-Contaminated Water.

Microbial degradation is a cost-effective and environmentally friendly method for removing microcystin-LR (MC-LR). However, the application of free bacteria has limitations due to low operational stability and difficulties in recovery. In a previous study, our group successfully isolated a highly efficient MC-LR-degrading bacterium, Sphingopyxis sp. YF1, from Taihu. To enhance its practical potential in addressing MC-LR-contaminated water pollution, a novel biological material named polyacrylonitrile-based carbon fiber @Sphingopyxis sp. YF1 (PAN-CF@YF1) was synthesized. The immobilization conditions of strain Sphingopyxis sp. YF1 on PAN-CF surfaces were optimized using Box-Behnken design and response surface methodology (RSM), which turned out to be an optimal pH of 7.6 for the culture medium, a ratio of 0.038 g of supporting materials per 100 mL of culture media, and an incubation time of 53.4 h. The resultant PAN-CF@YF1 showed a great degradation effect both for low and high concentrations of MC-LR and exhibited satisfactory cyclic stability (85.75% after six cycles). Moreover, the application of PAN-CF@YF1 in the bioreactors demonstrated effective and sustainable MC-LR removal, with a removal efficiency of 78.83% after three consecutive treatments. Therefore, PAN-CF@YF1 with high degradation activity, environmental compatibility, straightforward preparation, and recyclability shows significant application potential for the bioremediation of MC-LR-contaminated water bodies.

Phage-host interactions: The neglected part of biological wastewater treatment.

In wastewater treatment plants (WWTPs), the stable operation of biological wastewater treatment is strongly dependent on the stability of associated microbiota. Bacteriophages (phages), viruses that specifically infect bacteria and archaea, are highly abundant and diverse in WWTPs. Although phages do not have known metabolic functions for themselves, they can shape functional microbiota via various phage-host interactions to impact biological wastewater treatment. However, the developments of phage-host interaction in WWTPs and their impact on biological wastewater treatment are overlooked. Here, we review the current knowledge regarding the phage-host interactions in biological wastewater treatment, mainly focusing on the characteristics of different phage populations, the phage-driven changes in functional microbiota, and the potential driving factors of phage-host interactions. We also discuss the efforts required further to understand and manipulate the phage-host interactions in biological wastewater treatment. Overall, this review advocates more attention to the phage dynamics in WWTPs.

Characteristics, Prognosis, and Competing Risk Nomograms of Cutaneous Malignant Melanoma: Evidence for Pigmentary Disorders.

Purpose: Cutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM. Methods: We reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models. Results: The analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p < 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p < 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index >0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM. Conclusion: Patients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.

Growth Curves of Chinese Children with Androgen Insensitivity Syndrome: A Multicenter Registry Study.

Objective: To provide new information about androgen insensitivity syndrome (AIS), we studied growth patterns in Chinese children with AIS. Subjects: Data are from 118 untreated AIS patients who were admitted to eight pediatric endocrine centers from January 2010 to December 2019. Methods: In this retrospective cohort study, clinical data were collected from a multicenter database. We compared physical assessment data among AIS patients and standard growth charts for Chinese pediatric population. Results: 1. Children with AIS grew slightly less than the mean before 6 months of age, and then, height gradually increased before 12 years of age, from the median to +1 standard deviation (SD), according to the standard reference for Chinese pediatric population. After 12 years of age, height showed differently in profiles: The mean height in AIS patients gradually decreased from the mean to −1 SD, according to the standard for Chinese boys, and increased from the mean to +2 SD, according to the standard for Chinese girls. 2. The weights of children with AIS were greater than the mean standards of Chinese pediatric population from newborn to 11 years of age. From 12−16 years of age, the mean weight of children with AIS showed different profiles, from the mean to −1 SD, according to the standard for Chinese boys and from the mean to +1.5 SD, according to the standard for Chinese girls. 3. Weight standard deviation (WtSDS) and target height (THt) in northern Chinese AIS patients were significantly higher than those from the southern region (p = 0.035, 0.005, respectively). Age in northern Chinese AIS patients was significantly younger than those from the southern region (p = 0.034). No difference was found among birth weight (BW), birth length (BL), height standard deviation (HtSDS) and body mass index (BMI) in AIS patients from different regions (p > 0.05). 4. HtSDS and WtSDS in complete AIS (CAIS) patients were higher than those in partial AIS (PAIS) patients without significant difference (p > 0.05). Conclusions: Growth of children with AIS varied to different degrees. AIS patients seemed not to experience a puberty growth spurt. CAIS and PAIS patients show little difference in their growth. Regional differences have no effect on the height but influence the weight of AIS patients.

WNT5A promotes the metastasis of esophageal squamous cell carcinoma by activating the HDAC7/SNAIL signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, with high incidence and mortality rates and low survival rates. However, the detailed molecular mechanism of ESCC progression remains unclear. Here, we first showed significantly higher WNT5A and SNAIL expression in ESCC samples than in corresponding paracancerous samples. High WNT5A and SNAIL expression levels correlated positively with lymphatic metastasis and poor prognosis for patients with ESCC based on immunohistochemical (IHC) staining of 145 paired ESCC samples. Spearman's correlation analyses confirmed the strong positive correlation between WNT5A and SNAIL expression, and patients with ESCC presenting coexpression of WNT5A and SNAIL had the worst prognosis. Then, we verified that the upregulation of WNT5A promoted ESCC cell metastasis in vivo and in vitro, suggesting that WNT5A might be a promising therapeutic target for the prevention of ESCC. Furthermore, WNT5A overexpression induced the epithelial-mesenchymal transition via histone deacetylase 7 (HDAC7) upregulation, and HDAC7 silencing significantly reversed WNT5A-induced SNAIL upregulation and ESCC cell metastasis. In addition, we used HDAC7 inhibitors (SAHA and TMP269) to further confirm that HDAC7 participates in WNT5A-mediated carcinogenesis. Based on these results, HDAC7 is involved in WNT5A-mediated ESCC progression, and approaches targeting WNT5A and HDAC7 might be potential therapeutic strategies for ESCC.

Efficient photocatalytic inactivation of Microcystis aeruginosa by a novel Z-scheme heterojunction tubular photocatalyst under visible light irradiation.

The design of a photocatalyst for efficient algal inactivation under visible light is essential for the application of photocatalysis to the control of harmful algal blooms. In this study, a novel Z-scheme heterojunction tubular photocatalyst, Ag2O@PG, was synthesized by chemically depositing silver oxide compounded with P-doped hollow tubular graphitic carbon nitride for the photocatalytic inactivation of Microcystis aeruginosa (M. aeruginosa). The photocatalytic algal inactivation experiments showed that the photocatalytic activity of Ag2O@PG was influenced by the ratio of the composition of the obtained materials. The optimal algal inactivation efficiency was observed when using Ag2O@PG-0.4 at a dosage of 0.2 g/L. It was able to achieve a 99.1 % M. aeruginosa inactivation at an initial concentration of 4.5 × 106 cells/mL following 5 h' visible light irradiation. During the process, the cell membrane permeability and cell morphology changed. Furthermore, under the constant attack of superoxide radicals and holes caused by Ag2O@PG, the superoxide dismutase, glutathione and malondialdehyde of algae cells increased during the experiments to alleviate oxidative damage. Eventually, the antioxidant system of algae cells was destroyed. To further validate the potential application of Ag2O@PG-0.4 in real algal bloom environment, an experiment in real water samples was carried out. Overall, the Ag2O@PG-0.4 as an efficient photocatalyst has a promising potential for emergency treatment measures to alleviate algal blooms.

Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients.

Purpose: Congenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis. Methods: We retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis. Results: In 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients. Conclusion: Our study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.

Highly efficient catalytic hydrogenation of nitrophenols by sewage sludge derived biochar.

Finding a low cost and effective alternative to noble metal based catalyst has long been concerned in wastewater treatment and organic transformation. This work developed a highly efficient sewage sludge-based catalyst via a simple one-step pyrolysis method, and for the first time, applied it in the catalytic reduction of nitrophenols. Due to the higher content of graphitic nitrogen, abundant defect sites and low electron transfer resistance, sewage sludge derived biochar obtained at 800 °C (SSBC-800) exhibits the best catalytic performance, with the reaction rate of 0.48 min-1 and turnover frequency for 4-nitrophenol calculated to be 1.25 × 10-4 mmol•mg-1 min-1, which is comparable to or even superior than some reported noble metal-based catalyst. Moreover, SSBC-800 showed good recyclability of 90% 4-nitrophenol removal within 8 min after 4 runs, and maintained high catalytic activity in reduction of other substituent nitrophenols, such as 2-nitrophenol (0.54 min-1), 3-nitrophenol (0.61 min-1) and 2,4-dinitrophenol (0.18 min-1), and in real water samples, indicating its practical applicability. The electron paramagnetic resonance spectra and electrochemical characterization demonstrate that SSBC-800 accelerates the dissociation of BH4- to form active hydrogen, which is the main species responsible for 4-nitrophenol reduction, while electron transfer reaction involving the surface bound hydride derived from the intimate contact between BH4- and SSBC-800 plays an important role in this process. This research not only provides a novel valorization pathway for sewage sludge, but also sheds new light on further designing of carbon-based catalyst for nitrophenol reduction.

Soybean residue based biochar prepared by ball milling assisted alkali activation to activate peroxydisulfate for the degradation of tetracycline.

The advanced oxidation process (AOPs) has caused great concern in recent years. Among them, biochar has been widely studied as a catalyst for advanced oxidation process because of its low price and low environmental risk. In this study, a novel ball milling assisted KOH activation biochar (MKBC) was prepared and applied in peroxydisulfate (PDS) activation to degrade tetracycline hydrochloride (TC-H). In comparison with the oxidation (3.48%) by PDS alone and adsorption (36.19%) by MKBC alone, the removal rate of TC-H was increased to 84.15% in the MKBC/PDS system, indicating that MKBC can successfully activate PDS. Besides, the catalytic activity of the MKBC to activate PDS for the degradation of TC-H is 58.33% higher than that of pristine biochar (PBC). In addition, MKBC has outstanding stability that after three repeated experiments, the removal rate of TC-H by the MKBC/PDS system still remains 77.35%. Meanwhile, the mechanism was investigated that the singlet oxygen (1O2) seized the principal position in the degradation of TC-H in the PDS/MKBC system. This study explored a novel, solvent-free and economic method to propose this extraordinary biochar, which provided a new strategy for the future research of biochar.

Presence of microplastics in drinking water from freshwater sources: the investigation in Changsha, China.

We investigated the abundance of microplastics in freshwater, treated water, and household tap water from the drinking water supply chain in Changsha, China. The abundance was 2173-3998 (mean = 2753), 338-400 (mean = 351.9), and 267-404 (mean = 343.5) particles L-1 in freshwater, treated water, and tap water, respectively. Fibrous and fragments made up the majority (> 70%) in all water samples, and most polymers were composed of polyethylene, polypropylene, and polyethylene terephthalate. Microplastics in tap water were related to materials of transportation pipelines in drinking-water supply chain. Although plastics are corrosion-resistant, the slight fragmentation and abrasion may occur during drinking water treatment transportation. This study provided a proof for the occurrence of microplastics in drinking water, which may offer a reference for microplastic removal during drinking water treatment, and the formulation of standards for microplastic content in drinking water.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism.

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ±â€Š2.3 mL and 4.1 ±â€Š1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ±â€Š1.8 cm and 5.1 ±â€Š1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ±â€Š0.5 cm and 2.0 ±â€Š0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Benzyl butyl phthalate activates prophage, threatening the stable operation of waste activated sludge anaerobic digestion.

The stable operation of the anaerobic digestion of waste activated sludge (WAS) is threatened by numerous emerging contaminants. Meanwhile, the extensive microplastic pollution increased the environmental exposure risk of plasticizer benzyl butyl phthalate (BBP), the BBP content has reached a substantial level in WAS. However, the effect of BBP on WAS anaerobic digestion is still unknown. Here we show that high-level BBP brings on anaerobic digestion upset. The presence of 10.0 mg/L BBP (in sludge with 17,640 ± 510 mg/L TSS) led to deferred cell lysis, which was confirmed by the results of continuous parallel factor analysis of dissolved organic matter and the liberation of lactate dehydrogenase. Further, the deferred cell rupture was confirmed associate with prophage activation during WAS anaerobic digestion. Besides solubilization, the hydrolysis, acetogenesis and methanogenesis were also affected by the addition of BBP. The long-term effects of BBP revealed that the dominant microbial structure in anaerobic digester was stable, but the abundance of many functional microorganisms was changed, including short chain fatty acid producers and consumers. This work highlights one of the susceptibility mechanisms for WAS anaerobic digestion processes and provides new perspectives for the comprehensive assessment of emerging contaminant's environmental risks.