Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.

Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS.

miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2.

MiRNAs play an important role in spermatogonial stem cells (SSCs). The purpose of this study was to investigate the basic function of miR-22-5p in cryptorchidism. The results of RT-PCR, western blot, and immunohistochemistry showed that miR-22-5p was increased while EZH2 decreased in the testicular tissues of patients with cryptorchidism. Overexpression of miR-22-5p inhibited the proliferation of SSCs, increased cell apoptosis rate, and reduced expression of SSC marker proteins (GDNF and DAZL); however, knockout of miR-22-5p has the opposite effect. The Luciferase reporter gene assays demonstrated that EZH2 is a direct target of miR-22-5p. Moreover, EZH2 overexpression could reverse the effect of miR-22-5p mimic on SSCs' proliferation, apoptosis, and expression of SSC marker proteins. Our results demonstrated that miR-22-5p regulates SSCs' self-renewal by targeting EZH2, which indicated that miR-22-5p may serve as a biological marker for the treatment of infertility caused by cryptorchidism.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Factors shaping soil organic carbon stocks in grass covered orchards across China: A meta-analysis.

Orchard grass coverage has been widely adopted to increase fruit yield by improving soil fertility. However, the impact of the environment on the changes in soil organic carbon (SOC) stocks consecutive to orchard grass coverage remain poorly quantified at a large scale. The present study aimed to examine the responses of SOC stocks to grass coverage at a soil depth of 0-30 cm in orchards compared to clean tillage. A total of 342 observations across China from 139 peer-reviewed publications were subjected to meta-analysis. Aggregated boosted tree analysis was performed, evaluating the determinants of SOC stocks, such as plant traits (e.g., fruit tree type, grass type, orchard age, and grass age), edaphic variables (e.g., initial SOC and nitrogen concentration, soil pH, and soil clay content), climatic factors (e.g., mean annual precipitation (MAP) and mean annual temperature (MAT)), and management practices (e.g., grass source, grass growing mode, fertilization, grass mowing, placement of mowed residues, and irrigation). On average, orchard grass coverage significantly enhanced SOC stocks by 21.47% (percentage change) compared to clean tillage. Biotic and abiotic factors influenced this increase in SOC stocks following grass coverage in orchards to different extents. Grass age and soil clay content were the main determinants driving the variation in the SOC stocks following grass coverage in orchards. Thus, we propose an efficient way to optimize C sequestration in grass covered orchards, regarding plant traits, climatic factors, edaphic variables, and management practices. Longer than 12 months of surface grass coverage with cultivated grass species in mature deciduous fruit orchards (≥5 years) efficiently increased SOC stocks. This is particularly the case for acidic (pH < 6.5) soils with low C content (SOM < 15 g kg-1) in areas with suitable rainfall and temperature conditions (MAP ≥ 400 mm, MAT ≥ 10 °C). Collectively, this meta-analysis identified orchard grass coverage as a promising practice for significantly increasing SOC stocks at 0-30 cm across large geospatial locations in China.

Selenium-amended biochar mitigates inorganic mercury and methylmercury accumulation in rice (Oryza sativa L.).

Rice, as a dominant crop in China and Asia, can be a major route of methylmercury (MeHg) exposure for humans in inland China, especially in those living in mercury (Hg) polluted areas. Soil is the most prominent MeHg accumulation source for rice grains. The development of management practices to reduce MeHg in rice grains is crucial. This study explored the mitigation effect of biochar (BC) and sodium selenite-amended biochar (BC + Se) on MeHg production in paddy soil and accumulation in rice. Mercury-contaminated soil was treated with 1% and 5% of both BC and BC + Se. Soil MeHg concentration slightly increased under 1% BC/BC + Se compared to control soil but decreased at the rate of 5%. Moreover, soil phytoavailable MeHg (P-MeHg) diminished as the amount of Se-amended BC increased. BC + Se effectively mitigated MeHg accumulation in rice grains. The highest average contents of MeHg and inorganic Hg (IHg) in rice seeds were found in the control samples, followed by the 1%-BC, 5%-BC, 1%-BC + Se, and 5%-BC + Se samples. Under the 5%-BC + Se treatment, rice MeHg levels were reduced significantly (94%) compared to the control, and P-MeHg concentrations in soil were lower than all the other experimental groups throughout the rice-growing season. These results demonstrate the effectiveness of BC + Se in reducing MeHg and IHg accumulation in rice and could be employed for remediation of Hg polluted paddies.

Crop Production and Agricultural Carbon Emissions: Relationship Diagnosis and Decomposition Analysis.

Modern agriculture contributes significantly to greenhouse gas emissions, and agriculture has become the second biggest source of carbon emissions in China. In this context, it is necessary for China to study the nexus of agricultural economic growth and carbon emissions. Taking Jilin province as an example, this paper applied the environmental Kuznets curve (EKC) hypothesis and a decoupling analysis to examine the relationship between crop production and agricultural carbon emissions during 2000-2018, and it further provided a decomposition analysis of the changes in agricultural carbon emissions using the log mean Divisia index (LMDI) method. The results were as follows: (1) Based on the results of CO2 EKC estimation, an N-shaped EKC was found; in particular, the upward trend in agricultural carbon emissions has not changed recently. (2) According to the results of the decoupling analysis, expansive coupling occurred for 9 years, which was followed by weak decoupling for 5 years, and strong decoupling and strong coupling occurred for 2 years each. There was no stable evolutionary path from coupling to decoupling, and this has remained true recently. (3) We used the LMDI method to decompose the driving factors of agricultural carbon emissions into four factors: the agricultural carbon emission intensity effect, structure effect, economic effect, and labor force effect. From a policymaking perspective, we integrated the results of both the EKC and the decoupling analysis and conducted a detailed decomposition analysis, focusing on several key time points. Agricultural economic growth was found to have played a significant role on many occasions in the increase in agricultural carbon emissions, while agricultural carbon emission intensity was important to the decline in agricultural carbon emissions. Specifically, the four factors' driving direction in the context of agricultural carbon emissions was not stable. We also found that the change in agricultural carbon emissions was affected more by economic policy than by environmental policy. Finally, we put forward policy suggestions for low-carbon agricultural development in Jilin province.

Application of single-port video-assisted thoracoscope in treating thoracic oesophageal squamous cell carcinoma using McKeown approach.

OBJECTIVE: This study aims to investigate the feasibility of single-port video-assisted thoracoscope (SPVATS) in treating thoracic oesophageal squamous cell carcinoma (TESCC) using McKeown approach. MATERIALS AND METHODS: Totally 10 McKeown approach-based SPVATS surgeries (8 males and 2 females, aged 42-68 years) were carried out from January 2015 to December 2015 to treat TESCC, including one case in upper thoracic segment, 5 cases in median thoracic segment and 4 cases in inferior thoracic segment. All the cases were pathologically diagnosed as SCC pre-operatively. SPVATS was performed to free thoracic oesophagus and dissect the lymph nodes, and laparoscopy was performed to free stomach and to perform oesophagus-left gastric collum anastomosis. RESULTS: All the patients were successfully completed SPVATS, with average thoracic surgery time as 150 min, intra-operative blood loss as 30-260 ml (average 90 ml), and post-operative hospital stay as 9-16 days (average 12 days). CONCLUSIONS: SPVATS was technically feasible and safe in treating TESCC using McKeown approach, with less trauma and rapid post-operative recovery, and hence, it could be used as a new surgical option for McKeown approach-based TESCC treatment.

1.5 kW efficient CW Nd:YAG planar waveguide MOPA laser.

In this Letter, we report a 1064 nm continuous wave Nd:YAG planar waveguide laser with an output power of 1544 W based on the structure of the master oscillator power amplification. A fiber laser is used as the master oscillator, and diode laser arrays are used as the pump source of the waveguide laser amplifier. The dimension of the waveguide is 1 mm (T)×10 mm (W)×60 mm (L), and the dual end oblique pumping is adopted with different angles. After a single-pass amplification, the power is scaled from 323 to 1544 W with the pump power of 2480 W, leading to an optical-to-optical efficiency of 49%. At the maximum output, the beam quality M2 are measured to be 2.8 and 7.0 in the guided direction and the unguided direction, respectively. To the best of our knowledge, this is the highest output power of a Nd:YAG planar waveguide laser to date.

Significance of Upper Mediastinal Lymph Node Dissection with Video-Assisted Thoracic Surgery in the Treatment of Middle Thoracic Esophageal Carcinoma.

BACKGROUND: The aim of this study was to explore the significance of upper mediastinal lymph node dissection performed by video-assisted thoracic surgery in the treatment of middle thoracic esophageal carcinoma. MATERIALS AND METHODS: The clinical and pathological data from 128 patients with middle thoracic esophageal carcinoma who underwent surgery from January 2013 to December 2015 using a right chest-abdomen-neck approach combined with thoracoscopy and laparoscopy in the Jieyang People's Hospital of Huangdong province were analyzed retrospectively. RESULTS: The lymph node metastasis rates of the thoracic left para-recurrent laryngeal nerve (1, 2, and 4L zones) and right para-recurrent laryngeal nerve (1R zone) were 30.47% and 28.12% in 128 cases, respectively. The metastasis rates of the 2R, 4R, and 5 zones were 4.69%, 3.91%, and 5.47%, respectively. CONCLUSIONS: The upper mediastinal region was the most common location for lymph node metastasis from middle thoracic esophageal carcinoma, and upper mediastinal lymph node dissection performed by video-assisted thoracic surgery was safe and complete. It also reduced the risk of para-recurrent laryngeal nerve injury, residual tumor, and the postoperative recurrence rate.

High-efficiency, high-average-power, CW Yb:YAG zigzag slab master oscillator power amplifier at room temperature.

We demonstrate a high-efficiency, high-average-power, CW master oscillator power amplifier based on a conduction-cooled, end-pumped Yb:YAG slab architecture at room temperature (RT). Firstly, the CW amplification property is theoretically analyzed based on the kinetics model for Yb:YAG. To realize high-efficiency laser amplification extraction for RT Yb:YAG, not only intense pump but also a high-power seed laser is of great importance. Experimentally, a composite Yb:YAG crystal slab with three doped and two un-doped segments symmetrically is employed as the gain medium, which is end-pumped by two high-power, 940-nm diode lasers. A high-power, narrow-spectral-width, 1030-nm fiber seed laser then double passes the composite slab to realize efficient power amplification. For 0.8-kW seed input, maximum output power of 3.54 kW is obtained at 6.7 kW of pump power, with the optical conversion efficiency of 41% and the highest slope efficiency of 59%. To the best of our knowledge, this is the highest power and efficiency reported for Yb:YAG lasing at RT except thin-disk lasers.