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Objective To study the effects of different pellet feed hardness on the growth and reproduction, feed utilization rate, and environmental dust in laboratory mice. Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups, with an equal number of males and females. They were fed diets with different hardness of 18.62 kg, 23.15 kg, and 27.89 kg. Body weight, feed utilization rate, and dust levels in cages were recorded and calculated for mice aged 3-10 weeks. Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels. After 2 weeks of adaptation to the same hardness feed, the mice were paired at a 1∶2 male-to-female ratio and monitored for reproductive data for 3 months. Results At the age of 4 weeks, the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups (P0.05). For both strains, feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age (P0.05). However, the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness, while that of ICR mice increased with increasing feed hardness, though these differences were not statistically significant (P>0.05). Conclusion Different strains and genders had different tolerance to feed hardness. C57BL/6JGpt mice are more adapted to lower hardness feeds, while ICR mice are better suited to slightly higher hardness feeds.

Abstract The photocatalytic conversion of CO2 into solar‐powered fuels is viewed as a forward‐looking strategy to address energy scarcity and global warming. This work demonstrated the selective photoreduction of CO2 to CO using ultrathin Bi12O17Cl2 nanosheets decorated with hydrothermally synthesized bismuth clusters and oxygen vacancies (OVs). The characterizations revealed that the coexistences of OVs and Bi clusters generated in situ contributed to the high efficiency of CO2–CO conversion (64.3 μmol g−1 h−1) and perfect selectivity. The OVs on the facet (001) of the ultrathin Bi12O17Cl2 nanosheets serve as sites for CO2 adsorption and activation sites, capturing photoexcited electrons and prolonging light absorption due to defect states. In addition, the Bi‐cluster generated in situ offers the ability to trap holes and the surface plasmonic resonance effect. This study offers great potential for the construction of semiconductor hybrids as multiphotocatalysts, capable of being used for the elimination and conversion of CO2 in terms of energy and environment.

Abstract The semi‐hydrogenation of alkyne to form Z‐olefins with high conversion and high selectivity is still a huge challenge in the chemical industry. Moreover, flammable and explosive hydrogen as the common hydrogen source of this reaction increases the cost and danger of industrial production. Herein, we connect the photocatalytic hydrogen evolution reaction and the semi‐hydrogenation reaction of alkynes in series and successfully realize the high selective production of Z‐alkenes using low‐cost, safe, and green water as the proton source. Before the cascade reaction, a series of isomorphic metal–organic cage catalysts (CoxZn8−xL6, x = 0, 3, 4, 5, and 8) are designed and synthesized to improve the yield of the photocatalytic hydrogen production. Among them, Co5Zn3L6 shows the highest photocatalytic activity, with a H2 generation rate of 8.81 mmol g−1 h−1. Then, Co5Zn3L6 is further applied in the above tandem reaction to efficiently reduce alkynes to Z‐alkenes under ambient conditions, which can reach high conversion of >98% and high selectivity of >99%, and maintain original catalytic activity after multiple cycles. This “one‐pot” tandem reaction can achieve a highly selective and safe stepwise conversion from water into hydrogen into Z‐olefins under mild reaction conditions.

Abstract Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single‐component dual‐functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)‐generated HOCl. A representative prodrug (DHU‐CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU‐CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU‐CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase‐2 (COX‐2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX‐2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU‐CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single‐component dual‐functional prodrug activated by TME‐specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX‐2 inhibitor.

Abstract Water inflow is one of the main geohazards that threaten the safety of tunnels and other underground engineering projects. Faulted zone is one of the important geological triggers for such events. Numerical investigations on the evolution of flow behavior in tunnels across fault zones are of significance to the predication and prevention of this type of geohazards. In this work, a numerical investigation model with two overlapped parallel faults is established at a steady stage according to the "Three Zones" fault structure theory. The rapid turbulent flow in the fault zone is simulated by using the improved Darcy-Brinkman seepage model, while the slow laminar flow in ordinary rock zone is described by Darcy equation. The effect of relative position and distance between the tunnel excavation face and overlapped parallel faults to the groundwater pore pressure and flow velocity is studied through several scenarios, and the water inflow rate into the tunnel is calculated. The numerical investigation results reveal that while the tunnel face is excavated into the fault center core, the fractured zone, the ordinary rock zone, and the center of the overlapped faults, the pore pressure value ahead of the excavation face increases while the flow velocity decreases sequentially. The inflow rate is the largest while the tunnel face is excavated to center of the fault center core, which is closely related to the range of the overlapped area. The investigation results offer a practical reference for predicting early warning of water inflow geohazard when a tunnel cross two overlapped parallel faults.

While China’s clean air actions implemented since 2013 have been effective in mitigating PM _2.5 air pollution, the large emission reductions during the COVID-19 lockdown period in early 2020 did not similarly alleviate PM _2.5 pollution in North China, reflecting a distinct nonlinear chemical response of PM _2.5 formation to emission changes. Here we apply emission-concentration relationships for PM _2.5 diagnosed using the adjoint approach to quantitatively assess how chemical nonlinearity affects PM _2.5 over Beijing in February 2020 in response to two emission reduction scenarios: the COVID-19 lockdown and 2013–2017 emission controls. We find that, in the absence of chemical nonlinearity, the COVID-19 lockdown would decrease PM _2.5 in Beijing by 17.9 μ g m ^–3 , and the 2013–2017 emission controls resulted in a larger decrease of 54.2 μ g m ^–3 because of greater reductions of SO _2 and primary aerosol emissions. Chemical nonlinearity offset the decrease for Beijing PM _2.5 by 3.4 μ g m ^–3 during the lockdown due to enhanced sensitivity of aerosol nitrate to NO _x emissions, but enhanced the efficiency of 2013–2017 emission controls by 11.9 μ g m ^–3 due to the weakened heterogeneous reaction of sulfate. Such nonlinear chemical effects are important to estimate and consider when designing or assessing air pollution control strategies.

MicroRNA (miRNA) has vital regulatory effects on the proliferation, differentiation and secretion of ovarian granulosa cells, but the role of miR-99a-5p in goat ovarian granulosa cells (GCs) is unclear. Both miR-99a-5p and Frizzled-5 (FZD5) were found to be expressed in GCs in goat ovaries via fluorescence in situ hybridization and immunohistochemistry, respectively, and FZD5 was verified (P

The aim of this study was to evaluate the benefits and safety of transperitoneal and retroperitoneal pyeloplasty for ureteropelvic junction obstruction by a meta-analysis. We searched the databases including PubMed, Cochrane Library and Embase database from their inception to December 1st, 2020. Relevant literatures comparing retroperitoneal pyeloplasty with transperitoneal pyeloplasty were identified. A meta-analysis was conducted with Revman 5.3. The main outcomes included success rate, operative time, hospital stay, conversion rate of open surgery, overall complications, and detailed postoperative complications/indicators. 15 studies with 1881 patients were included. The results revealed that there were no significant differences between two approaches in success rate [OR = 1.51, 95%CI (0.94, 2.41), p = 0.09], hospital stay [MD = 0.21, 95%CI (−0.12, 0.54), p = 0.21] and overall complications [OR = 1.07, 95%CI (0.76, 1.50), p = 0.69]. The retroperitoneal approach was associated with longer operative time [MD = −26.91, 95%CI (−40.97, −12.84), p

Accurate wind speed forecasting is very crucial for wind power generation systems, but the inherent randomness of wind speeds makes wind speed forecasting challenging. There have been many studies on predicting wind speeds, but they ignored the influence factor of wind speed on its change over time with multiple factors, such as wind direction, temperature, humidity and atmospheric pressure. Therefore, a secondary factor induced wind speed time series prediction using self-adaptive interval type-2 fuzzy sets (IT2FS) with error correction was proposed. First, an IT2FS model is developed to induce secondary factors to predict wind speed. Specifically, the differential evolution algorithm is employed to optimize parameters of IT2FS model. Second, error correction strategy is adopted to correct the model error. The auto-regressive integrated moving average model is used to predict the residual sub-sequence after variational mode decomposition. Finally, by predicting the wind speed of two wind farms in China, it is verified that the proposed hybrid system transcends other compared models and simultaneously realizes high accuracy and strong stability. Thus, employing a new strategy to conduct the main factor time series prediction using its secondary factors is extremely useful for enhancing the prediction performance.

Objective: The aim was to evaluate the efficacy and safety of vancomycin or daptomycin (VAN/DAP), antistaphylococcal β-lactam (ASBL), trimethoprim-sulfamethoxazole (TMP-SMX), and combination therapy of VAN/DAP + ASBL in the management of methicillin-resistant Staphylococcus aureus (MRSA).Methods: Databases including PubMed, Cochrane Library, Embase database, and google scholar were searched on 1 September 2021. The randomized control trials (RCTs) and comparable clinical studies of VAN/DAP, VAN/DAP + ASBL, ASBL, and TMP-SMX in the management of MRSA were identified. A network meta-analysis was conducted with STATA 14.0.Results: Seven RCTs and two matched cohorts with 1,048 patients were included in the analysis. The pooled results showed that VAN/DAP + ASBL had a significantly lower rate of persistent bacteremia >3 days than VAN/DAP alone [OR:0.46, 95%CI (0.26, 0.81), p < 0.001]. No obvious differences were observed in the outcomes of all-cause mortality, relapsed bacteremia, microbiological treatment failure, embolic or metastatic infection, and total adverse events. However, the ranking results showed that VAN/DAP + ASBL had slightly better efficacy (all-cause mortality, persistent bacteremia >3 days, duration of bacteremia, microbiological treatment failure, and relapsed bacteremia) but slightly higher adverse events than VAN/DAP alone. No obvious differences in the comparisons of VAN/DAP vs. ASBL, and VAN/DAP vs TMP-SMX in the analyzed outcomes. The ranking results revealed that ASBL and TMP-SMX did not have better efficacy or lower adverse events compared with the treatment of VAN/DAP.Conclusion: The efficacy of VAN/DAP + ASBL was slightly but not significantly better than VAN/DAP alone in the management of MRSA.

Objective: This study aimed to evaluate the survival outcomes of patients with bladder outlet obstruction (BOO) and metastatic prostate cancer (mPCa) after having a palliative transurethral resection of the prostate (pTURP) surgery.Methods: We identified patients with mPCa between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received pTURP and non-surgical therapy were identified. A propensity-score matching was introduced to balance the covariate. Kaplan–Meier analysis and COX regression were conducted to evaluate the overall survival (OS) and cancer-specific survival (CSS) outcomes.Results: A total of 36,003 patients were identified; 2,823 of them were in the pTURP group and 33,180 were in the non-surgical group. The survival curves of the overall cohort showed that the pTURP group was associated with worse outcomes in both OS (HR: 1.12, 95% CI: 1.07–1.18, p < 0.001) and CSS (HR: 1.08, 95% CI: 1.02–1.15, p = 0.004) compared with the non-surgical group. The mean survival time in the overall cohort of the pTURP group was shorter than the non-surgical group in both OS [35.13 ± 1.53 vs. 40.44 ± 0.59 months] and CSS [48.8 ± 1.27 vs. 55.92 ± 0.43 months]. In the matched cohort, the pTURP group had significantly lower survival curves for both OS (HR: 1.25, 95% CI: 1.16–1.35, p < 0.001) and CSS (HR: 1.23, 95% CI: 1.12–1.35, p < 0.001) than the non-surgical group. pTURP significantly reduced the survival months of the patients (36.49 ± 0.94 vs. 45.52 ± 1.23 months in OS and 50.1 ± 1.49 vs. 61.28 ± 1.74 months in CSS). In the multivariate COX analysis, pTURP increased the risk of overall mortality (HR: 1.19, 95% CI: 1.09–1.31, p < 0.001) and cancer-specific mortality CSS (HR: 1.23, 95% CI: 1.14–1.33, p < 0.001) compared with the non-surgical group.Conclusions: For mPCa patients with BOO, pTURP could reduce OS and CSS while relieving the obstruction.

Abstract Objectives To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance 3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x109/L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator and are able to swallow capsules or tablets. The complete inclusion and exclusion criteria as detailed in the Additional file 1 should be fulfilled. Drug specific inclusion and exclusion criteria will also be applied to the active arms. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres in the UK including initially at Cambridge University Hospitals NHS Foundation Trust and St George’s University NHS Foundation Trust. Other centres will be approached internationally in view of the evolving pandemic. Intervention and comparator There is increasing evidence of the role of immunomodulation in altering the course of COVID-19. Additionally, various groups have demonstrated the presence of pulmonary shunting in patients with COVID-19 as well as other cardiovascular complications. TACTIC-E will assess the efficacy of the novel immunomodulatory agent EDP1815 versus the approved cardio-pulmonary drugs, Dapagliflozin in combination with Ambrisentan versus the prevailing standard of care. EDP1815 will be given as 2 capsules twice daily (1.6 x 1011 cells) for up to 7 days with the option to extend up to 14 days at the discretion of the principal investigator or their delegate, if the patient is felt to be clinically responding to treatment, is tolerating treatment, and is judged to be likely to benefit from a longer treatment course. Ambrisentan 5mg and Dapagliflozin 10mg will be given in combination once daily orally for up to maximum of 14 days. Patients will be randomised in a 1:1:1 ratio across treatments. Each active arm will be compared with standard of care alone. Additional arms may be added as the trial progresses. No comparisons will be made between active arms in this platform trial. Main outcomes The primary outcome is the incidence (from baseline up to Day 14) to the occurrence of the any one of the following events: death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance

Phase field method was used to simulate the effect of grains orientation angle θ11 and azimuth θA of non-preferentially growing dendrites on the secondary dendrites of preferentially growing dendrites. In the simulation process, two single-factor influence experiments were designed for columnar crystal structures. The simulation results showed that, when θ11 < 45º and θA < 45º, as θ11 was enlarged, the growth direction of the secondary dendrites on the preferentially growing dendrites at the converging grain boundary (GB) presented an increasing inclination to that of preferentially growing dendrites; with increasing θA, the growth direction of the secondary dendrites on the preferentially growing dendrites at the converging GB exhibited greater deflection, and the secondary dendrites grew with branches; the secondary dendrites on the preferentially growing dendrites at diverging GBs grew along a direction vertical to the growth direction of the preferentially growing dendrites. When θA = 45º and θ11 = 45º, the secondary dendrites grew in a direction vertical to the growth direction of preferentially growing dendrites. The morphologies of the dendrites obtained through simulation can also be found in metallographs of practical solidification experiments. This implies that the effect of a grain’s orientation angle and azimuth of non-preferentially growing dendrites on the secondary dendrites of preferentially growing dendrites does exist and frequently appears in the practical solidification process.

Taking Al-2%mole-Cu binary alloy as an example, the infl uence of grain orientation on competitive growth of dendrites under different competitive modes was investigated by using the three-dimensional (3-D) phasefi eld method. The result of phase-fi eld simulation was verifi ed by applying cold spray and directional remelting. In the simulation process, two competitive modes were designed: in Scheme 1, the monolayer columnar grains in multilayer columnar crystals had different orientations; while in Scheme 2, they had the same orientation. The simulation result showed that in Scheme 1, the growth of the dendrites, whose orientation had a certain included angle with the direction of temperature gradient, was restrained by the growth of other dendrites whose direction was parallel to the direction of temperature gradient. Moreover, the larger the included angle between the grain orientation and temperature gradient, the earlier the cessation of dendrite growth. The secondary dendrites of dendrites whose grain orientation was parallel to the temperature gradient fl ourished with increasing included angles between the grain orientation and temperature gradient. In Scheme 2, the greater the included angle between grain orientation and temperature gradient, the easier the dendrites whose orientation showed a certain included angle with temperature gradient inserted between those grew parallel to the temperature gradient, and the better the growth condition thereafter. Some growing dendrites after intercalation were defl ected to the temperature gradient, and the greater the included angle, the lower the defl ection. The morphologies of the competitive growth dendrites obtained through simulation can also be found in metallographs of practical solidification experiments. This implies that the two modes of competitive growth of dendrites characterized in the simulation do exist and frequently appear in practical solidifi cation processes.

The intrinsic endpoint effect of empirical mode decomposition (EMD) will lead to serious divergence of the intrinsic mode function (IMF) at the endpoint, which will lead to the distortion of IMF and affect the decomposition accuracy of EMD. In view of this phenomenon, an EMD endpoint effect suppression method based on boundary local feature scale adaptive matching extension was proposed. This method can consider both the change trend of the signal at the endpoint and the change rule of the signal inside. The simulation results showed that the proposed method had better suppression effect on the intrinsic endpoint effect of EMD than the traditional EMD endpoint effect suppression method and achieved high-precision IMF. The endpoint effect suppression method of EMD based on boundary local feature scale adaptive matching extension was used to process the actual blasting seismic signal. The decomposition results showed that the method can effectively suppress the endpoint effect of EMD of blasting seismic signal and are helpful to extract the detailed characteristic parameters of blasting seismic signal.