Promoting the efficiency and selectivity of NO3--to-NH3 reduction on Cu-O-Ti active sites via preferential glycol oxidation with holes.

The combined reductive and oxidative reaction is the essence of a solar-driven photoredox system. Unfortunately, most of these efforts focus on the specific half-reactions, and the key roles of complete photoredox reactions have been overlooked. Taking the nitrate reduction reaction (NO3-RR) as a typical multiple-electrons involved process, the selective reduction of the NO3- into ammonia (NH3) synthesis with high efficiency is still a grand challenge. Herein, a rational oxidative half-reaction is tailored to achieve the selective conversion of NO3- to NH3 on Cu-O-Ti active sites. Through the coupled NO3-RR with glycol oxidation reaction system, a superior NH3 photosynthesis rate of 16.04 ± 0.40 mmol gcat-1 h-1 with NO3- conversion ratio of 100% and almost 100% of NH3 selectivity is reached on Cu-O-Ti bimetallic oxide cluster-anchored TiO2 nanosheets (CuOx@TNS) catalyst. A combination of comprehensive in situ characterizations and theoretical calculations reveals the molecular mechanism of the synergistic interaction between NO3-RR and glycol oxidation pair on CuOx@TNS. The introduction of glycol accelerates the h+ consumption for the formation of alkoxy (•R) radicals to avoid the production of •OH radicals. The construction of Cu-O-Ti sites facilitates the preferential oxidation of glycol with h+ and enhances the production of e- to participate in NO3-RR. The efficiency and selectivity of NO3--to-NH3 synthesis are thus highly promoted on Cu-O-Ti active sites with the accelerated glycol oxidative half-reaction. This work upgrades the conventional half photocatalysis into a complete photoredox system, demonstrating the tremendous potential for the precise regulation of reaction pathway and product selectivity.

Contribution of platelets to disruption of the blood-brain barrier during arterial baroreflex dysfunction.

BACKGROUND: Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption. METHODS: ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction. RESULTS: Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel. CONCLUSION: During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.

Regulating the Selectivity of Nitrate Photoreduction for Purification or Ammonia Production by Cooperating Oxidative Half-Reactions.

The removal and conversion of nitrate (NO3-) from wastewater has become an important environmental and health topic. The NO3- can be reduced to nontoxic nitrogen (N2) for environmental remediation or ammonia (NH3) for recovery, in which the tailoring of the selectivity is greatly challenging. Here, by construction of the CuOx@TiO2 photocatalyst, the NO3- conversion efficiency is enhanced to ∼100%. Moreover, the precise regulation of selectivity to NH3 (∼100%) or N2 (92.67%) is accomplished by the synergy of cooperative redox reactions. It is identified that the selectivity of the NO3- photoreduction is determined by the combination of different oxidative reactions. The key roles of intermediates and reactive radicals are revealed by comprehensive in situ characterizations, providing direct evidence for the regulated selectivity of the NO3- photoreduction. Different active radicals are produced by the interaction of oxidative reactants and light-generated holes. Specifically, the introduction of CH3CHO as the oxidative reactant results in the generation of formate radicals, which drives selective NO3- reduction into N2 for its remediation. The alkyl radicals, contributed to by the (CH2OH)2 oxidation, facilitate the deep reduction of NO3- to NH3 for its upcycling. This work provides a technological basis for radical-directed NO3- reduction for its purification and resource recovery.

A study on genotypes and phenotypes of short stature caused by epigenetic modification gene variants.

Mendelian disorders of the epigenetic machinery (MDEMs) are caused by genetic mutations, a considerable fraction of which are associated with epigenetic modification. These MDEMs exhibit phenotypic overlap broadly characterized by multiorgan abnormalities. The variant detected in genes associated with epigenetic modification can lead to short stature accompanied with multiple system abnormalities. This study is aimed at presenting and summarizing the diagnostic rate, clinical, and genetic profile of MDEMs-associated short stature. Two hundred and fourteen short-stature patients with multiorgan abnormalities were enrolled. Clinical information and whole exome sequence (WES) were analyzed for these patients. WES identified 33 pathogenic/likely pathogenic variants in 19 epigenetic modulation genes (KMT2A, KMT2D, KDM6A, SETD5, KDM5C, HUWE1, UBE2A, NIPBL, SMC1A, RAD21, CREBBP, CUL4B, BPTF, ANKRD11, CHD7, SRCAP, CTCF, MECP2, UBE3A) in 33 patients (15.4%). Of note, 19 variants had never been reported previously. Furthermore, these 33 variants were associated with 16 different disorders with overlapping clinical features characterized by development delay/intelligence disability (31/33; 93.9%), small hands (14/33; 42.4%), clinodactyly of the 5th finger (14/33; 42.4%), long eyelashes (13/33; 39.4%), and hearing impairment (9/33; 27.3%). Additionally, several associated phenotypes are reported for the first time: clubbing with KMT2A variant, webbed neck with SETD5 variant, retinal detachment with CREBBP variant, sparse lateral eyebrow with HUWE1 variant, and long palpebral fissure with eversion of the lateral third of the low eyelid with SRCAP variant.Conclusions: Our study provided a new conceptual framework for further understanding short stature. Specific clinical findings may indicate that a short-stature patient may have an epigenetic modified gene variant.

Dynamic in situ Formation of Cu2 O Sub-Nanoclusters through Photoinduced pseudo-Fehling's Reaction for Selective and Efficient Nitrate-to-Ammonia Photosynthesis.

Copper (Cu) is evidenced to be effective for constructing advanced catalysts. In particular, Cu2 O is identified to be active for general catalytic reactions. However, conflicting results regarding the true structure-activity correlations between Cu2 O-based active sites and efficiencies are usually reported. The structure of Cu2 O undergoes dynamic evolution rather than remaining stable under working conditions, in which the actual reaction cannot proceed over the prefabricated Cu2 O sites. Therefore, the dynamic construction of Cu2 O active sites can be developed to promote catalytic efficiency and reveal the true structure-activity correlations. Herein, by introducing the redox pairs of Cu2+ and reducing sugar into a photocatalysis system, it is clarified that the Cu2 O sub-nanoclusters (NCs), working as novel active sites, are on-site constructed on the substrate via a photoinduced pseudo-Fehling's route. The realistic interfacial charge separation and transformation capacities are remarkably promoted by the dynamic Cu2 O NCs under the actual catalysis condition, which achieves a milestone efficiency for nitrate-to-ammonia photosynthesis, including the targets of production rate (1.98±0.04 mol gCu -1 h-1 ), conversion ratio (94.2±0.91 %), and selectivity (98.6 %±0.55 %). The current work develops an effective strategy for integrating the active site construction into realistic reactions, providing new opportunities for Cu-based chemistry and catalysis sciences research.

Continuous NO Upcycling into Ammonia Promoted by SO2 in Flue Gas: Poison Can Be a Gift.

Although ammonia (NH3) synthesis efficiency from the NO reduction reaction (NORR) is significantly promoted in recent years, one should note that NO is one of the major air pollutants in the flue gas. The limited NO conversion ratio is still the key challenge for the sustainable development of the NORR route, which potentially contributes more to contaminant emissions rather than its upcycling. Herein, we provide a simple but effective approach for continuous NO reduction into NH3, promoted by coexisting SO2 poison as a gift in the flue gas. It is significant to discover that SO2 plays a decisive role in elevating the capacity of NO absorption and reduction. A unique redox pair of SO2-NO is constructed, which contributes to the exceptionally high conversion ratio for both NO (97.59 ± 1.42%) and SO2 (99.24 ± 0.49%) in a continuous flow. The ultrahigh selectivity for both NO-to-NH3 upcycling (97.14 ± 0.55%) and SO2-to-SO42- purification (92.44 ± 0.71%) is achieved synchronously, demonstrating strong practicability for the value-added conversion of air contaminants. The molecular mechanism is revealed by comprehensive in situ technologies to identify the essential contribution of SO2 to NO upcycling. Besides, realistic practicality is realized by the efficient product recovery and resistance ability against various poisoning effects. The proposed strategy in this work not only achieves a milestone efficiency for NH3 synthesis from the NORR but also raises great concerns about contaminant resourcing in realistic conditions.

Beyond Purification: Highly Efficient and Selective Conversion of NO into Ammonia by Coupling Continuous Absorption and Photoreduction under Ambient Conditions.

Although the selective catalytic reduction technology has been confirmed to be effective for nitrogen oxide (NOx) removal, green and sustainable NOx re-utilization under ambient conditions is still a great challenge. Herein, we develop an on-site system by coupling the continuous chemical absorption and photocatalytic reduction of NO in simulated flue gas (CNO = 500 ppm, GHSV = 18,000 h-1), which accomplishes an exceptional NO conversion into value-added ammonia with competitive conversion efficiency (89.05 ± 0.71%), ammonia production selectivity (95.58 ± 0.95%), and ammonia recovery efficiency (>90%) under ambient conditions. The anti-poisoning capacities, including the resistance against factors of H2O, SO2, and alkali/alkaline/heavy metals, are also achieved, which presents strong environmental practicability for treating NOx in flue gas. In addition, the critical roles of corresponding chemical absorption and catalytic reduction components are also revealed by in situ characterizations. The emerging strategy herein not only achieves a milestone efficiency for sustainable NO purification but also opens a new route for contaminant resourcing in the near future of carbon neutrality.

Development and validation of a model for predicting the adult height of girls with idiopathic central precocious puberty.

The aim was to develop a model to predict the adult height (AH) of idiopathic central precocious puberty (ICPP) girls who underwent gonadotropin-releasing hormone analog (GnRHa) treatment. Data analysis included 258 girls with ICPP. Among them, 101 girls who reached final AH (FAH) with GnRHa treatment were analyzed to verify three previous prediction models and develop a unique model based on multiple linear regression. The control group consisted of 41 untreated ICPP girls. Moreover, 116 girls treated with GnRHa who almost attained FAH were included for external validation. Based on our cohorts, all of the three previously published models underestimated the FAH with an R of 0.667, 0.793, and 0.664. The AH prediction model was built as follows: Calculated AH (cm) = 1.89630 * Height SDS + 2.29927 * Height SDS for bone age + 0.40776 * Target height + 100.16684 (R2 = 0.66 and adjusted R2 = 0.65). Internal validation showed a mean root mean squared error (RMSE) of 2.16 cm and a mean absolute error (MAE) of 1.64 cm. External validation showed that a significant error (> 1 SD) appeared only in 7 of 116 girls (6.0%). The model is displayed on the website: http://cpppredict.shinyapps.io/dynnomapp . CONCLUSION: A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. WHAT IS KNOWN: • Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. WHAT IS NEW: • This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study.

Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Precocious puberty or growth hormone deficiency as initial presentation in Mayer-Rokitansky-kuster-Hauser syndrome: a clinical report of 5 cases.

BACKGROUND: We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency (GHD. Our five children add to the growing endocrine data base of MRKHS. CASE PRESENTATION: We retrospectively reviewed clinical data of 5 MRKHS patients from 2017 to 2020. The clinical features, hormonal profiles, radiological imaging and genetic analyses were collated. The age range of the 5 patients at diagnosis was 6.7-9.1 years. Four presented with premature thelarche, and one presented with short stature. External genitalia were normal in all patients. Gonadotropin-releasing hormone stimulation tests for the 5 patients revealed peak luteinizing hormone and follicular stimulating hormone levels of 3.57, 6.24, 11.5, 4.44 and 4.97 IU/L and 9.41, 16.7, 13.8, 14.2 and 10.3 mIU/mL, respectively. Growth hormone stimulation for one patient with short stature was consistent with GHD with a peak level of GH was 7.30 ng/mL. Imaging disclosed advanced bone age in four patients and no skeletal abnormalities in any of the patients. Ultrasonography of the abdomen revealed bilateral polycystic kidneys in one patient. Pelvic magnetic resonance imaging confirmed no uterus in five patients. All of the patients had a normal karyotype (46, XX). In one patient, whole-exome sequencing detected a deletion of 17q12(chr17:36,046,434-36,105,050, hg19) encompassing the HNF1B gene. CONCLUSIONS: We report the unusual co-occurrence of precocious puberty and GHD in patients with MRKHS, highlighting that abnormal puberty and growth development may represent initial unexplained manifestations. Whether the deletion of 17q 22 begat GHD is unclear.

Low-Altitude Infrared Slow-Moving Small Target Detection via Spatial-Temporal Features Measure.

Robust detection of infrared slow-moving small targets is crucial in infrared search and tracking (IRST) applications such as infrared guidance and low-altitude security; however, existing methods easily cause missed detection and false alarms when detecting infrared small targets in complex low-altitude scenes. In this article, a new low-altitude slow-moving small target detection algorithm based on spatial-temporal features measure (STFM) is proposed. First, we construct a circular kernel to calculate the local grayscale difference (LGD) in a single image, which is essential to suppress low-frequency background and irregular edges in the spatial domain. Then, a short-term energy aggregation (SEA) mechanism with the accumulation of the moving target energy in multiple successive frames is proposed to enhance the dim target. Next, the spatial-temporal saliency map (STSM) is obtained by integrating the two above operations, and the candidate targets are segmented using an adaptive threshold mechanism from STSM. Finally, a long-term trajectory continuity (LTC) measurement is designed to confirm the real target and further eliminate false alarms. The SEA and LTC modules exploit the local inconsistency and the trajectory continuity of the moving small target in the temporal domain, respectively. Experimental results on six infrared image sequences containing different low-altitude scenes demonstrate the effectiveness of the proposed method, which performs better than the existing state-of-the-art methods.

The role of the gut microbiota on the metabolic status of obese children.

BACKGROUND: The term "metabolically healthy obese (MHO)" denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator. OBJECTIVE: This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic statuses, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6, TNF-α, lipopolysaccharide-binding protein (LBP), and a cytokine up-regulator and mediator, leptin. RESULTS: Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n = 42), metabolic unhealthy obese (MUO, n = 23), and healthy normal weight controls (Con, n = 21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO group, Spearman's correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, LBP was positively correlated with genus Roseburia and Faecalibacterium, and negatively correlated with genus Lactobacillus, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p < 0.05). CONCLUSION: Although there are distinct differences in the characteristic gut microbiota of the MUO population versus MHO, dysbiosis of gut microsystem is already extant in the MHO cohort. The abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds, suggesting that dysbiosis of gut microbiota, present in the MHO children, conceivably serves as a compensatory or remedial response to a surfeit of nutrients.

Stretchable Nanolayered Thermoelectric Energy Harvester on Complex and Dynamic Surfaces.

Thermoelectric generators (TEGs) provide a unique solution for energy harvesting from waste heat, presenting a potential solution for green energy. However, traditional rigid and flexible TEGs cannot work on complex and dynamic surfaces. Here, we report a stretchable TEG (S-TEG) (over 50% stretchability of the entire device) that is geometrically suitable for various complex and dynamic surfaces of heat sources. The S-TEG consists of hot-pressed nanolayered p-(Sb2Te3) and n-(Bi2Te3)-type thermoelectric couple arrays and exploits the wavy serpentine interconnects to integrate all units. The internal resistance of a 10 × 10 array is 22 ohm, and the output power is ∼0.15 mW/cm2 at ΔT = 19 K on both developable and nondevelopable surfaces, which are much improved compared with those of existing S-TEGs. The energy harvesting of S-TEG from the dynamic surfaces of the human skin offers a potential energy solution for the wearable devices for health monitoring.

[Expert consensus for the diagnosis and treatment of glutaricacidemia type 1].

Glutaricacidemia type 1(GA1) is an autosomal recessive disease caused by reduced or missing glutaryl-CoA dehydrogenase activity which hamps metabolism of lysine, hydroxylysine and tryptophan. The catabolic products of glutarylcarnitine and glutaric acid are abnormally accumulated in the body, resulting in metabolic disorders which primarily lead to damage to the nervous system. Clinical manifestations of patients include macrocephaly, dystonia, dyskinesia, and developmental retardation. Acute encephalopathy may be induced in infants and young children due to infection, vaccination and surgery. For GA1 is a rare disease and its clinical manifestations are similar to other neurological diseases, it may be easily missed or misdiagnosed. To facilitate early diagnosis and treatment and improve the prognosis, this consensus was formulated by pediatric experts from the fields of endocrinology and genetic metabolism through full discussion and reference to the latest literature and guidelines home and abroad.

Clinical features, genetic detection and therapeutic response to rhGH of children with Noonan syndrome: an analysis of 12 cases.

To analyze the clinical manifestations, genetic features and therapeutic efficacy of patients with Noonan syndrome (NS). The clinical data of 12 NS children treated in Fuzhou Children' Hospital of Fujian Medical University from September 2015 to April 2021 were analyzed. Among them, 7 patients with height lower than two standard deviations of the mean (or below the third percentile) were treated with recombinant human growth hormone (rhGH), and were followed up every The clinical characteristics were as following: facial anomalies (=12), short stature (=11), congenital heart diseases (=5), facial freckles (=4), coffee spots on the skin (=3), intelligence disability (=3),cryptorchidism (=3), feeding difficulties (=2), scoliosis (=2), pectus carinatum (=2), pectus excavatum (=1), rib dysplasia companied with short finger (=1), hyperopia (=1), myopia (=1) and early puberty (=1). The mutation was detected in 10 cases, mutation was detected in 1 case, and mutation was detected in 1 case. In 7 patients treated with rhGH, the mean height velocity increased from before treatment to after treatment for (<0.01); the height velocity was the fastest during 3 to of treatment, and then gradually went slower. The serum levels of insulin-like growth factor 1 (IGF-1) remained within the normal range. The clinical manifestations of NS are diverse, and the disease can be diagnosed through genetic testing. For NS patients with short stature, rhGH treatment can increase the height velocity and no obvious adverse reactions were found.

Gut microbiota: effect of pubertal status.

BACKGROUND: The make-up of gut microbiota at different puberty stages has not been reported. This cross-sectional study analyzed the bio-diversity of gut microbiota at different puberty stages. RESULT: The subjects (aged 5-15 years) were divided into non-pubertal (n = 42, male%: 66.7%) or pubertal groups (n = 47, male%:44.68); in both groups, Firmicutes, Bacteroidetes and Proteobacteria were the dominant phylum. There was no difference of alpha- and beta-diversity among disparate puberty stages. Non-pubertal subjects had members of the order Clostridiales, family Clostridiaceae, genus Coprobacillus which were significantly more prevalent than puberty subjects. Also, the pubertal subjects had members of class Betaproteobacteria, order Burkholderiales which were significantly more prevalent than the non-pubertal subjects. Their relative abundance was independent of BMI-Z. In the pubertal subjects, the abundance of genus Adlercreutzia, Ruminococcus, Dorea, Clostridium and Parabacteroides was associated with the level of testosterone. CONCLUSIONS: This is the first report of the diversity of gut microbiota at different puberty stages. The various species of gut microbiota changed gradually associated with puberty stages. Differences in gut microflora at different pubertal status may be related to androgen levels.

High-speed wide-field multi-parametric photoacoustic microscopy.

Capable of imaging blood perfusion, oxygenation, and flow simultaneously at the microscopic level, multi-parametric photoacoustic microscopy (PAM) has quickly emerged as a powerful tool for studying hemodynamic and metabolic changes due to physiological stimulations or pathological processes. However, the low scanning speed poised by the correlation-based blood flow measurement impedes its application in studying rapid microvascular responses. To address this challenge, we have developed a new, to the best of our knowledge, multi-parametric PAM system. By extending the optical scanning range with a cylindrically focused ultrasonic transducer (focal zone, 76µm×4.5mm) for simultaneous acquisition of 500 B-scans, the new system is 112 times faster than our previous multi-parametric system that uses a spherically focused transducer (focal diameter, 40 µm) and enables high-resolution imaging of blood perfusion, oxygenation, and flow over an area of 4.5×1mm2 at a frame rate of 1 Hz. We have demonstrated the feasibility of this system in the living mouse ear. Further development of this system into reflection mode will enable real-time cortex-wide imaging of hemodynamics and metabolism in the mouse brain.

Sexual dimorphism of gut microbiota at different pubertal status.

BACKGROUND: Accumulating evidence infer that gut microbiome-host relations are key mediators or modulators driving the observed sexual dimorphism in some disease onset and progression. To date, the sex-differences of gut microbiota at different pubertal status have not been reported. OBJECTIVE: To determine the characteristics of gut microbiota of both genders at different pubertal status. METHODS: Gut microbiota was analyzed in 89 Chinese participants aged 5-15 years. Participants were divided into pre-puberty and puberty groups for both male and female. The composition of gut microbiota was investigated by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed. The prediction of metagenomic functional content from 16S rRNA gene surveys was conducted. RESULTS: There were 49 males (9.76 ± 2.15 years) and 40 females (9.74 ± 1.63 years); 21 males and 26 females were at puberty. At genus level, Alistipes, Megamonas, Oscillospira and Parabacteroides were more prevalent in girls than in boys (p < 0.05). There were no significantly differences of alpha-diversity between genders, which was independent of pubertal status. The beta-diversity was significantly different in pubertal subjects between genders. Using statistical analyses, we assigned genera Dorea, Megamonas, Bilophila, Parabacteroides and Phascolarctobacterium as microbial markers for pubertal subjects. The predicted metabolic profiles differ in both pubertal and pre-pubertal groups between genders. CONCLUSION: This cross-sectional study revealed that sex differences in the gut microbiota composition and predicted metabolic profiles exist before puberty, which become more significant at puberty. The identification of novel puberty bacterial markers may disclose a potential effects of gender-related microbiota profiles on puberty onset.

New insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype-phenotype profiling of SRD5A2 in 190 Chinese patients.

BACKGROUND: The 5α-reductase type 2 (5α-RD2) deficiency caused by mutations in the steroid 5α-reductase 2 (SRD5A2) gene results in variable degrees of undervirilisation in patients with 46,XY disorders of sex development. This study aims to profile the regional distribution and phenotype-genotype characteristics of SRD5A2 in a large Chinese 5α-RD2 deficiency cohort through multi-centre analysis. METHODS: 190 subjects diagnosed with 5α-RD2 deficiency were consecutively enrolled from eight medical centres in China. Their clinical manifestations and genetic variants were analysed. RESULTS: Hypospadias (isolated or combined with microphallus and/or cryptorchidism) was fairly common in the enrolled subjects (66.32%). 42 variants, including 13 novel variants, were identified in SRD5A2. Homozygous and compound heterozygous mutations presented in 38.42% and 61.58% of subjects, respectively, and predominated in exons 1, 4 and 5. The most prevalent variant was c.680G > A (52.37%), followed by c.16C > T, (10.79%), c.607G > A, (9.21%) and c.737G > A, (8.95%). However, their distributions were different: c.680G > A was more common in South China than in North China (62.62% vs 39.16%, p < 0.001), whereas the regional prevalence of c.16C > T was reversed (6.07% vs 16.87%, p = 0.001). Furthermore, c.680G > A prevailed in cases with normal meatus (68.75%) or distal hypospadias (66.28%), compared with those with proximal hypospadias (35.54%, p < 0.001). However, cases with proximal hypospadias showed a higher frequency of c.16C > T (20.48%) than those with normal meatus (3.13%) or distal hypospadias (3.49%, p < 0.001). CONCLUSIONS: This study profiled variable phenotypic presentation and wide mutational spectrum of SRD5A2, revealing its distinctive regional distribution in Chinese patients and further shaping the founder effect and genotype-phenotype correlation of SRD5A2.