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Lonicerae japonicae Flos (LJF) is a natural plant containing abundant antioxidant ingredients. In order to extract more antioxidants from LJF, in this study, a novel strategy was proposed for optimizing the extraction factor level by response surface methodology with a tailored deep eutectic solvent (DES) as the extraction solvent and antioxidant ability as the evaluation index. After optimizing the composition of DES and the extraction condition, the extracts obtained by our proposed method yielded better antioxidant ability (229.1–249.1 μmol TE/g DW) and higher antioxidant contents (34.2–36.5 mg GAE/g DW for total phenolics and 119.6–123.0 mg RE/g DW for total flavonoids) from LJF in 5 min without organic solvent consumption that were significantly superior to the Chinese Pharmacopoeia extraction method. The K-T solvation parameter and a scanning electron microscope were adopted to explore the extraction mechanism, and the results showed that the polarity and damage effect on plant cells of DES were crucial for the extraction of antioxidants. In addition, after combining the HPLC fingerprint and partial least squares model, chlorogenic acid, rutin, and 3,5-O-Dicaffeoylquinic acid were screened as the antioxidant Q-markers of LJF. This work demonstrates that an optimization strategy based on antioxidant ability and tailored DES has the potential to extract more antioxidants from natural plants. [ABSTRACT FROM AUTHOR]

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol. [ABSTRACT FROM AUTHOR]

Background: Previous investigations have shown a positive relationship between baseball pitching velocity and the kinetic chain involved in pitching motion. However, no study has examined the influence of finger characteristics on pitching velocity and rate of spin via a sensor-embedded baseball. Methods: Twenty-one pitchers volunteered and were recruited for this study. An experimental baseball embedded with a force sensor and an inertial measurement unit was designed for pitching performance measurement. Finger length and strength were measured as dependent variables. Spin rate and velocity were independent variables. Pearson product–moment correlations (r) and intraclass correlation coefficients (ICCs) determined the relationship between finger characteristics and pitching performance. Results: Finger length discrepancy, two-point pinch strength, index finger RFD (rate of force development), middle finger impulse, and force discrepancy had significant correlations with spin rate (r = 0.500~0.576, p ≤ 0.05). Finger length discrepancy, two-point pinch, three-point pinch strength, index and middle finger RFD, middle finger impulse, and force combination had significant correlations with fastball pitching velocity (r = 0.491~0.584, p ≤ 0.05). Conclusions: Finger length discrepancy, finger pinch strength, and pitching finger force including maximal force and RFD may be factors that impact fastball spin rate and fastball pitching velocity. [ABSTRACT FROM AUTHOR]

Reported herein is a Paternò–Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at −78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics. [ABSTRACT FROM AUTHOR]

Enhancing cross-protections against diverse influenza viruses is desired for influenza vaccinations. Neuraminidase (NA)-specific antibody responses have been found to independently correlate with a broader influenza protection spectrum. Here, we report a sequential immunization regimen that includes priming with NA protein followed by boosting with peptide nanoclusters, with which targeted enhancement of antibody responses in BALB/c mice to certain cross-protective B-cell epitopes of NA was achieved. The nanoclusters were fabricated via desolvation with absolute ethanol and were only composed of composite peptides. Unlike KLH conjugates, peptide nanoclusters would not induce influenza-unrelated immunity. We found that the incorporation of a hemagglutinin peptide of H2-d class II restriction into the composite peptides could be beneficial in enhancing the NA peptide-specific antibody response. Of note, boosters with N2 peptide nanoclusters induced stronger serum cross-reactivities to heterologous N2 and even heterosubtypic N7 and N9 than triple immunizations with the prototype recombinant tetrameric (rt) N2. The mouse challenge experiments with HK68 H3N2 also demonstrated the strong effectiveness of the peptide nanocluster boosters in conferring heterologous protection. [ABSTRACT FROM AUTHOR]

Simple Summary: A previous study found that an indigenous endoparasitic wasp Cotesia ruficrus, has a good control effect on the invasive pest Spodoptera frugiperda. Understanding the molecular mechanism of host recognition of C. ruficrus would help improve its biological control effect. Chemoreceptor proteins (CSPs) play a crucial role in insect olfactory perception. The CrufCSP1 protein was obtained via prokaryotic expression, and its binding properties were evaluated using fluorescence binding assays. Molecular docking was used to verify the function of CrufCSP1. The findings revealed that CrufCSP1 has the ability to bind with seven host-related compounds. This information serves as a crucial reference for developing natural enemy attractants for pest control. Chemosensory proteins (CSPs) are a class of soluble proteins that facilitate the recognition of chemical signals in insects. While CSP genes have been identified in many insect species, studies investigating their function remain limited. Cotesia ruficrus (Hymenoptera: Braconidae) holds promise as an indigenous biological control agent for managing the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae) in China. This study aimed to shed light on the gene expression, ligand binding, and molecular docking of CrufCSP1 in C. ruficrus. A RT-qPCR analysis revealed that the expression of CrufCSP1 was higher in the wings, with male adults exhibiting significantly higher relative expression levels than other developmental stages. A fluorescence competitive binding analysis further demonstrated that CrufCSP1 has a high binding ability with several host-related volatiles, with trans-2-hexenal, octanal, and benzaldehyde showing the strongest affinity to CrufCSP1. A molecular docking analysis indicated that specific amino acid residues (Phe24, Asp25, Thr53, and Lys81) of CrufCSP1 can bind to these specific ligands. Together, these findings suggest that CrufCSP1 may play a crucial role in the process of C. ruficrus locating hosts. This knowledge can contribute to the development of more efficient and eco-friendly strategies for protecting crops and managing pests. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last twenty years, minimally invasive surgery (MIS) has radically changed the surgical landscape. In the field of thoracic surgery, approaches such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) have become the new standards for the majority of procedures performed, especially for early-stage lung cancer. Despite these developments, there is still a lack of concrete data regarding treatment outcomes of these minimally invasive approaches compared to the conventional open surgery. In the future, the number of minimally invasive procedures will likely keep increasing as more lung cancer nodules are detected at early stages due to lung cancer screening initiatives. Therefore, data on short- and long-term outcomes of VATS and RATS in early-stage lung cancer is needed. In the last two decades, robotic-assisted thoracoscopic surgery (RATS) has gained popularity as a minimally invasive surgical (MIS) alternative to multi- and uniportal video-assisted thoracoscopic surgery (VATS). With this approach, the surgeon obviates the known drawbacks of conventional MIS, such as the reduced in-depth perception, hand-eye coordination, and freedom of motion of the instruments. Previous studies have shown that a robotic approach for operable lung cancer has treatment outcomes comparable to other MIS techniques such as multi-and uniportal VATS, but with less blood loss, a lower conversion rate to open surgery, better lymph node dissection rates, and improved ergonomics for the surgeon. The thoracic surgeon of the future is expected to perform more complex procedures. More patients will enter a multimodal treatment scheme making surgery more difficult due to severe inflammation. Furthermore, due to lung cancer screening programs, the number of patients presenting with operable smaller lung nodules in the periphery of the lung will increase. This, combined with the fact that segmentectomy is becoming an increasingly popular treatment for small peripheral lung lesions, indicates that the future thoracic surgeons need to have profound knowledge of segmental resections. New imaging techniques will help them to locate these lesions and to achieve a complete oncologic resection. Current robotic techniques exist to help the thoracic surgeon overcome these challenges. In this review, an update of the latest MIS approaches and nodule detection techniques will be given. [ABSTRACT FROM AUTHOR]

The structural characteristics of an urban road network directly affect the urban road network's overall function and service level. Because the hierarchical division and layout form of an urban road network has self-similarity and scale invariance, the urban traffic network has certain time-space fractal characteristics, and fractal theory has become a powerful tool for evaluating traffic networks. This paper calculates and compares five fractal dimensions (FD) of nine districts in Harbin. Meanwhile, each calculated FD is linearly regressed with the area, population, built-up area, building area, the total number and length of roads, and the number of buildings in the region. The results show that the fractal dimensions of the five types are between 1 and 2. In the same district, the values of the FD perimeter and FD ruler are lower compared to the FD box, FD information, and FD mass, whereas those of the FD box and FD information are higher. Compared to the FD box and FD information, the value of FD mass shows unevenly. Based on the current research results, this study discusses the feasibility of using relevant indicators in the fractal process to evaluate the layout of the urban road network and guide its optimization and adjustment. [ABSTRACT FROM AUTHOR]

The use of heat pipes (HP) for the DEMO in-vessel plasma-facing components (PFCs) has been considered because of their high capacity to transport the heat from a heat source to a heat sink by means of the vaporization and condensation of the working fluid inside and their ability to enlarge the heat transfer area of the cooling circuit substantially. Recent engineering studies conducted in the framework of the EUROfusion work package Divertor (Wen et al, 2021) indicate that it is possible to design a heat pipe with a capillary limit above 6 kW using a composite capillary structure (wherein axial grooves cover the adiabatic zone and the condenser, and sintered porous material covers the evaporator). This power level would correspond to an applied heat flux of 20 MW/m², rendering such a design interesting with respect to a divertor target concept. To validate the results of the initial engineering analysis, several experiments have been conducted to evaluate the actual performance of the proposed heat pipe concept. The present contribution presents the experiment's results regarding the examination of the operating limits of two different designs for an evaporator: one featuring a plain porous structure, and one featuring ribs and channels. [ABSTRACT FROM AUTHOR]

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions—association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty—we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization. [ABSTRACT FROM AUTHOR]

Prolactinomas have been reported to impair cognition in broad aspects. However, few studies investigated the influence of prolactinomas on cognitive flexibility never mentioning the underlying neural and electrophysiological mechanism. We recorded scalp electroencephalography (EEG) in a colour-shape switching task. Patients with prolactinomas showed longer reaction time in switch trials and larger switch costs relative to healthy controls (HCs). Compared to HCs who showed stronger frontal theta activity in switch trials, the generally weak frontal theta activity in patients implied that they could not afford the executive control to configure task sets. Meanwhile, machine-learning based classification revealed that patients manifested non-selective brain patterns in response to different task types (colour vs. shape task) and different task states (switch vs. repeat state), which collectively suggested the cognitive dysfunction in preparation for a changing environment. Compared to HCs who showed stronger frontoparietal synchronization in switch trials, this enhanced frontoparietal connectivity was disrupted among patients with severe prolactinomas. This finding implicated greater hyperprolactinemia was linked to a larger decrease in cognitive performance. Taken together, the present study highlighted frontal theta power, and frontoparietal connectivity at theta band as the electrophysiological markers of the impaired cognitive flexibility and task control in patients with prolactinomas. [ABSTRACT FROM AUTHOR]

(1) Background: Hypertensive patients with obstructive sleep apnea (OSA) are at high risk for cardiovascular diseases (CVDs), and the utility of aspirin for primary cardiovascular prevention in this population remains uncertain. (2) Methods: In this retrospective cohort study using data from the Urumchi Hypertension Database (UHDATA), hypertensive patients older than 18 years old with a first-time diagnosis of OSA were divided into three groups depending on aspirin history. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included MACCE components, ischemic events, cardiac events, cerebrovascular events, and gastrointestinal bleeding risk. The inverse probability of treatment weighting (IPTW) method was used to balance the confounding factors among the groups, and the Cox proportional hazards model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). (3) Results: In persistent aspirin users, the risk of MACCE events (HR 2.11, 95%CI 1.23–3.63), ischemic events (HR 2.58, 95%CI 1.42–4.69), cerebrovascular events (HR 2.55, 95%CI 1.44–4.51), and non-fatal cerebral infarction (HR 3.14, 95%CI 1.69–5.84) was significantly elevated. (4) Conclusions: Continuous aspirin use increases the incidence of cardiovascular adverse events in hypertensive patients with OSA receiving aspirin for primary prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named "ion induction and deduction" was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple "net-hubs" and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research. [ABSTRACT FROM AUTHOR]

Chemicals underlying the floral aroma of dry teas needs multi-dimensional investigations. Green, black, and freeze-dried tea samples were produced from five tea cultivars, and only 'Chunyu2' and 'Jinguanyin' dry teas had floral scents. 'Chunyu2' green tea contained the highest content of total volatiles (134.75 μg/g) among green tea samples, while 'Jinguanyin' black tea contained the highest content of total volatiles (1908.05 μg/g) among black tea samples. The principal component analysis study showed that 'Chunyu2' and 'Jinguanyin' green teas and 'Chunyu2' black tea were characterized by the abundant presence of certain alcohols with floral aroma, while 'Jinguanyin' black tea was discriminated due to the high levels of certain alcohols, esters, and aldehydes. A total of 27 shared volatiles were present in different tea samples, and the contents of 7 floral odorants in dry teas had correlations with those in fresh tea leaves (p < 0.05). Thus, the tea cultivar is crucial to the floral scent of dry tea, and these seven volatiles could be promising breeding indices. [ABSTRACT FROM AUTHOR]

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates. [ABSTRACT FROM AUTHOR]

This paper presents a case study of a lithium battery and fuel cell integrated powertrain system for a renewable energy vehicle. The performance analysis includes evaluating the energy consumption of the vehicle and the efficiency of the power generation components. When driven solely by the lithium battery at average speeds of 15 km/h and 20 km/h, it was observed that speed significantly influences the travel distance of the vehicle, with higher speeds resulting in lower mileage. The energy efficiency rates were found to be 89.3% and 85.7% at speeds of 15 km/h and 20 km/h, respectively, indicating an 18.1% decrease in efficiency from low to higher speeds. When the lithium battery is solely charged by the hydrogen fuel cell, the efficiency under test conditions reaches approximately 32.5%. In the "FC + B + SC" driving mode, which combines the use of the lithium battery, fuel cell, and solar panel to power the vehicle, the travel range can be extended to 50.62 km and 42.05 km, respectively, representing an increase of over 50%, with overall efficiencies of 63.8% and 60.7%, respectively. This hybrid powertrain system exhibits rapid dynamic response, high energy and power density, and enables longer travel distances for the renewable energy vehicle. [ABSTRACT FROM AUTHOR]

This paper puts forward a joint optimization algorithm of task assignment and flight path planning for a heterogeneous unmanned aerial vehicle (UAV) cluster in a multi-mission scenario (MMS). The basis of the proposed algorithm is to establish constraint and threat models of a heterogeneous UAV cluster to simultaneously minimize range and maximize value gain and survival probability in an MMS under the constraints of task payload, range, and task requirement. On one hand, the objective function for the heterogeneous UAV cluster within an MMS is derived and it is adopted as a metric for assessing the performance of the joint optimization in task assignment and flight path planning. On the other hand, since the formulated joint optimization problem is a multi-objective, non-linear, and non-convex optimization model due to its multiple decision variables and constraints, the roulette wheel selection (RWS) principle and the elite strategy (ES) are introduced in an ant colony optimization (ACO) to solve the complex optimization model. The simulation results indicate that the proposed algorithm is superior and more efficient compared to other approaches. [ABSTRACT FROM AUTHOR]

The synthesis of 2-aminoquinazoline derivatives is achieved by using hydrochloric acid as a mediator in the [4+2] annulation reaction between N-benzyl cyanamides and 2-amino aryl ketones. In addition, 2-amino-4-iminoquinazolines are synthesized by the reaction of 2-aminobenzonitriles, instead of 2-amino aryl ketones, with N-benzyl cyanamides. A wide range of substrates can be used and high yields are obtained, demonstrating the practicality of this method for the synthesis of 2-aminoquinazoline derivatives. [ABSTRACT FROM AUTHOR]

The extensive and close economic linkages among different regions of China have effects not only on regional economic growth, but also on CO2 emissions and carbon leakage among regions. Taking Beijing as a study case, we constructed MRIO models for China's 30 provinces and municipalities for 2002, 2007 and 2010, to measure the embodied CO2 emissions in the interregional trade of China on regional and industrial levels to explore their changes over time, and to analyze the driving forces of the final demand-induced interregional CO2 emissions through an SDA model. Results showed that Beijing was a surplus region for embodied carbon and the net input embodied CO2 emissions were in industries with high CO2 emission coefficients, while the net output embodied carbon was in industries with low carbon-emission coefficients. Beijing's trade with non-Beijing areas led to an increase in the total CO2 emissions in China and a composite effect of Beijing and the efficiency effect of non-Beijing areas were the main effects behind the reduction of Beijing's input embodied carbon. The results have yielded important implications for China's CO2 emissions control: first, the embodied CO2 need be taken into consideration when formulating CO2 emissions control measures; second, CO2 emission reduction requirements should be reasonably distributed across the provinces to reduce carbon leakage in interprovincial trade; third, the consumption structure in the production chain needs to be moderately adjusted; and last but not least, financial and technical support for CO2 emissions control in the central and western provinces should be strengthened. [ABSTRACT FROM AUTHOR]

Despite the acceptance of carotid ultrasound for predicting patients' fluid responsiveness in critical care and anesthesia, its efficacy for predicting hypotension and fluid responsiveness remains unclear in the perioperative setting. Electronic databases were searched from inception to May 2023 to identify observational studies focusing on the use of corrected blood flow time (FTc) and respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak) for assessing the risks of hypotension and fluid responsiveness. Using FTc as a predictive tool (four studies), the analysis yielded a pooled sensitivity of 0.82 (95% confidence interval (CI): 0.72 to 0.89) and specificity of 0.94 (95% CI: 0.88 to 0.97) for the risk of hypotension (area under curve (AUC): 0.95). For fluid responsiveness, the sensitivity and specificity of FTc were 0.79 (95% CI: 0.72 to 0.84) and 0.81 (95% CI: 0.75 to 0.86), respectively (AUC: 0.87). In contrast, the use of ΔVpeak to predict the risk of fluid responsiveness showed a pooled sensitivity of 0.76 (95% CI: 0.63 to 0.85) and specificity of 0.74 (95% CI: 0.66 to 0.8) (AUC: 0.79). The current meta-analysis provides robust evidence supporting the high diagnostic accuracy of FTc in predicting perioperative hypotension and fluid responsiveness, which requires further studies for verification. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the association between hematocrit (HCT) levels and all-cause mortality in geriatric hip fractures. Methods: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of these patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between HCT levels and mortality. Analyses were performed using EmpowerStats and the R software. Results: A total of 2589 patients were included in this study. The mean follow-up period was 38.94 months. Eight hundred and seventy-five (33.8%) patients died due to all-cause mortality. Linear multivariate Cox regression models showed that HCT level was associated with mortality (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.96–0.99, p = 0.0002) after adjusting for confounding factors. However, the linear association was unstable and nonlinearity was identified. A HCT level of 28% was the inflection point for prediction. A HCT level of <28% was associated with mortality (HR = 0.91, 95% CI: 0.87–0.95, p < 0.0001), whereas a HCT level > 28% was not a risk factor for mortality (HR = 0.99, 95% CI: 0.97–1.01, p = 0.3792). We found that the nonlinear association was very stable in the propensity score-matching sensitivity analysis. Conclusions: The HCT level was nonlinearly associated with mortality in geriatric hip fracture patients and could be considered a predictor of mortality in these patients. Registration: ChiCTR2200057323. [ABSTRACT FROM AUTHOR]

Hydrogen with high energy content is considered to be a promising alternative clean energy source. Biohydrogen production through microbes provides a renewable and immense hydrogen supply by utilizing raw materials such as inexhaustible natural sunlight, water, and even organic waste, which is supposed to solve the two problems of "energy supply and environment protection" at the same time. Hydrogenases and nitrogenases are two classes of key enzymes involved in biohydrogen production and can be applied under different biological conditions. Both the research on enzymatic catalytic mechanisms and the innovations of enzymatic techniques are important and necessary for the application of biohydrogen production. In this review, we introduce the enzymatic structures related to biohydrogen production, summarize recent enzymatic and genetic engineering works to enhance hydrogen production, and describe the chemical efforts of novel synthetic artificial enzymes inspired by the two biocatalysts. Continual studies on the two types of enzymes in the future will further improve the efficiency of biohydrogen production and contribute to the economic feasibility of biohydrogen as an energy source. [ABSTRACT FROM AUTHOR]

As essential calcium ion (Ca2+) sensors in plants, calcium-dependent protein kinases (CDPKs) function in regulating the environmental adaptation of plants. However, the response mechanism of CDPKs to salt stress is not well understood. In the current study, the wheat salt-responsive gene TaCDPK27 was identified. The open reading frame (ORF) of TaCDPK27 was 1875 bp, coding 624 amino acids. The predicted molecular weight and isoelectric point were 68.905 kDa and 5.6, respectively. TaCDPK27 has the closest relationship with subgroup III members of the CDPK family of rice. Increased expression of TaCDPK27 in wheat seedling roots and leaves was triggered by 150 mM NaCl treatment. TaCDPK27 was mainly located in the cytoplasm. After NaCl treatment, some of this protein was transferred to the membrane. The inhibitory effect of TaCDPK27 silencing on the growth of wheat seedlings was slight. After exposure to 150 mM NaCl for 6 days, the NaCl stress tolerance of TaCDPK27-silenced wheat seedlings was reduced, with shorter lengths of both roots and leaves compared with those of the control seedlings. Moreover, silencing of TaCDPK27 further promoted the generation of reactive oxygen species (ROS); reduced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); aggravated the injury to photosystem II (PS II); and increased programmed cell death (PCD) in wheat leaves under NaCl treatment, confirming that the TaCDPK27-silenced seedlings exhibited more NaCl injury than control seedlings. Taken together, the decrease in NaCl tolerance in TaCDPK27-silenced seedlings was due to excessive ROS accumulation and subsequent aggravation of the NaCl-induced PCD. TaCDPK27 may be essential for positively regulating salt tolerance in wheat seedlings. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation. [ABSTRACT FROM AUTHOR]

Whole-body vibration (WBV) is commonly applied in exercise and rehabilitation and its safety issues have been a major concern. Vibration measured using accelerometers can be used to further analyze the vibration transmissibility. Optimal bending angles and rating of perceived exertion (RPE) evaluations have not been sufficiently explored to mitigate the adverse effect. Therefore, the aims of this study were to investigate the effect of various knee flexion angles on the transmissibility to the head and knee, the RPE during WBV exposure, and the link between the transmissibility to the head and the RPE. Sixteen participants randomly performed static squats with knee flexion angles of 90, 110, 130, and 150 degrees on a WBV platform. Three accelerometers were fixed on the head, knee, and center of the vibration platform to provide data of platform-to-head and platform-to-knee transmissibilities. The results showed that the flexion angle of 110 degrees induced the lowest platform-to-head transmissibility and the lowest RPE (p < 0.01). A positive correlation between RPE and the platform-to-head transmissibility was observed. This study concluded that a knee flexion of about 110 degrees is most appropriate for reducing vibration transmissibility. The reported RPE could be used to reflect the vibration impact to the head. [ABSTRACT FROM AUTHOR]

Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment strategies to mitigate radiation injury is in pressing need. Recently, stem cell-based therapy generates great attention in clinical care. Among these, mesenchymal stem cells are extensively applied because it is easy to access and capable of mesodermal differentiation, immunomodulation, and paracrine secretion. Here, we summarize the current attempts and discuss the future perspectives about mesenchymal stem cells (MSCs) for mitigating radiotherapy side effects. [ABSTRACT FROM AUTHOR]

Drought and salinity stress are considered to be the two main factors limiting crop productivity. With climate change, these stresses are projected to increase, further exacerbating the risks to global food security. Consequently, to tackle this problem, better agricultural management is required on the basis of improved drought and salinity stress monitoring capabilities. Remote sensing makes it possible to monitor crop health at various spatiotemporal scales and extents. However, remote sensing has not yet been used to monitor both drought and salinity stresses simultaneously. The aim of this paper is to review the current ability of remote sensing to detect the impact of these stresses on vegetation indices (VIs) and crop trait responses. We found that VIs are insufficiently accurate (0.02 ≤ R2 ≤ 0.80) to characterize the crop health under drought and salinity stress. In contrast, we found that plant functional traits have a high potential to monitor the impacts of such stresses on crop health, as they are more in line with the vegetation processes. However, we also found that further investigations are needed to achieve this potential. Specifically, we found that the spectral signals concerning drought and salinity stress were inconsistent for the various crop traits. This inconsistency was present (a) between studies utilizing similar crops and (b) between investigations studying different crops. Moreover, the response signals for joint drought and salinity stress overlapped spectrally, thereby significantly limiting the application of remote sensing to monitor these separately. Therefore, to consistently monitor crop responses to drought and salinity, we need to resolve the current indeterminacy of the relationships between crop traits and spectrum and evaluate multiple traits simultaneously. Using radiative transfer models (RTMs) and multi-sensor frameworks allow monitoring multiple crop traits and may constitute a way forward toward evaluating drought and salinity impacts. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified tens of genetic variants associated with Parkinson's disease (PD). Nevertheless, the genes or DNA elements that affect traits through these genetic variations are usually undiscovered. This study was the first to combine meta-analysis GWAS data and expression data to identify PD risk genes. Four known genes, CRHR1, KANSL1, NSF and LRRC37A, and two new risk genes, STX4 and BST1, were identified. Among them, CRHR1 is a known drug target, indicating that hydrocortisone may become a potential drug for the treatment of PD. Furthermore, the potential pathogenesis of CRHR1 and LRRC37A was explored by applying DNA methylation (DNAm) data, indicating a pathogenesis whereby the effect of a genetic variant on PD is mediated by genetic regulation of transcription through DNAm. Overall, this research identified the risk genes and pathogenesis that affect PD through genetic variants, which has significance for the diagnosis and treatment of PD. [ABSTRACT FROM AUTHOR]

As non-viral transgenic vectors, the piggyBac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. However, further improvements in transpose activity are required for industrialization and clinical applications. Herein, we established a one-plasmid effective screening system and a two-step high-throughput screening process in yeast to isolate hyperactive mutants for mammalian cell applications. By applying this screening system, 15 hyperactive piggyBac transposases that exhibited higher transpose activity compared with optimized hyPBase in yeast and four mutants that showed higher transpose activity in mammalian cells were selected among 3000 hyPBase mutants. The most hyperactive transposase, bz-hyPBase, with four mutation sites showed an ability to yield high-efficiency editing in Chinese hamster ovarian carcinoma (CHO) cells and T cells, indicating that they could be expanded for gene therapy approaches. Finally, we tested the potential of this screening system in other versions of piggyBac transposase. [ABSTRACT FROM AUTHOR]

Here, we describe a mild, catalyst-free and operationally-simple strategy for the direct fluoroalkylation of olefins driven by the photochemical activity of an electron donor−acceptor (EDA) complex between DMA and fluoroalkyl iodides. The significant advantages of this photochemical transformation are high efficiency, excellent functional group tolerance, and synthetic simplicity, thus providing a facile route for further application in pharmaceuticals and life sciences. [ABSTRACT FROM AUTHOR]

The aim of this paper is to summarize and evaluate results from existing studies on accuracy and clinical value of three-dimensional printed heart models (3DPHM) for determining whether 3D printing can significantly improve on how the congenital heart disease (CHD) is managed in current clinical practice. Proquest, Google Scholar, Scopus, PubMed, and Medline were searched for relevant studies until April 2019. Two independent reviewers performed manual data extraction and assessed the risk of bias of the studies using the tools published on National Institutes of Health (NIH) website. The following data were extracted from the studies: author, year of publication, study design, imaging modality, segmentation software, utility of 3DPHM, CHD types, and dimensional accuracy. R software was used for the meta-analysis. Twenty-four articles met the inclusion criteria and were included in the systematic review. However, only 7 studies met the statistical requirements and were eligible for meta-analysis. Cochran's Q test demonstrated significant variation among the studies for both of the meta-analyses of accuracy of 3DPHM and the utility of 3DPHM in medical education. Analysis of all included studies reported the mean deviation between the 3DPHM and the medical images is not significant, implying that 3DPHM are highly accurate. As for the utility of the 3DPHM, it is reported in all relevant studies that the 3DPHM improve the learning experience and satisfaction among the users, and play a critical role in facilitating surgical planning of complex CHD cases. 3DPHM have the potential to enhance communication in medical practice, however their clinical value remains debatable. More studies are required to yield a more meaningful meta-analysis. [ABSTRACT FROM AUTHOR]

Many studies have demonstrated that berberine inhibited the cell migration and invasion in human cancer cell lines. However, the exact molecular mechanism of berberine inhibiting the cell migration and invasion of human melanoma A375.S2 and A375.S2/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains unknown. In this study, we investigated the anti-metastasis mechanisms of berberine in human melanoma cancer A375.S2 cells and A375.S2/PLX resistant cells in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 μM) induced cell morphological changes and reduced the viable cell number and inhibited the mobility, migration, and invasion of A375.S2 cells that were assayed by wound healing and transwell filter. The gelatin zymography assay showed that berberine slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N-cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1/2, p-c-Jun, p-FAK, p-AKT, NF-κB, and uPA after 24 h of treatment, but increased the PKC and PI3K in A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the treatment of cancer cells harboring activated BRAF mutations. Berberine decrease cell number and inhibited the cell mobility in the resistant A375.S2 (A375.S2/PLX, PLX4032 generated resistant A375.S2 cells). Based on these observations, we suggest that the potential of berberine as an anti-metastatic agent in melanoma that deserves to be investigated in more detail, including in vivo studies in future. [ABSTRACT FROM AUTHOR]

In patients with triple-negative breast cancer (TNBC)—the subtype with the poorest prognosis among breast cancers—it is crucial to assess the response to the currently widely employed neoadjuvant treatment (NAT) approaches. This study investigates the correlation between baseline conventional ultrasound (US) and shear-wave elastography (SWE) indicators and the pathological response of TNBC following NAT, with a specific focus on assessing predictive capability in the baseline state. This retrospective analysis was conducted by extracting baseline US features and SWE parameters, categorizing patients based on postoperative pathological grading. A univariate analysis was employed to determine the relationship between ultrasound indicators and pathological reactions. Additionally, we employed a receiver operating characteristic (ROC) curve analysis and multivariate logistic regression methods to evaluate the predictive potential of the baseline US indicators. This study comprised 106 TNBC patients, with 30 (28.30%) in a nonmajor histological response (NMHR) group and 76 (71.70%) in a major histological response (MHR) group. Following the univariate analysis, we found that T staging, dmax values, volumes, margin changes, skin alterations (i.e., thickening and invasion), retromammary space invasions, and supraclavicular lymph node abnormalities were significantly associated with pathological efficacy (p < 0.05). Combining clinical information with either US or SWE independently yielded baseline predictive abilities, with AUCs of 0.816 and 0.734, respectively. Notably, the combined model demonstrated an improved AUC of 0.827, with an accuracy of 76.41%, a sensitivity of 90.47%, a specificity of 55.81%, and statistical significance (p < 0.01). The baseline US and SWE indicators for TNBC exhibited a strong relationship with NAT response, offering predictive insights before treatment initiation, to a considerable extent. [ABSTRACT FROM AUTHOR]

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49–1.99; p = 4.07 × 10−11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20–1.74; p = 1.23 × 10−4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (−) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (−) subtype. [ABSTRACT FROM AUTHOR]

Doxorubicin is one of the most widely used antitumor drugs and is currently produced via the chemical conversion method, which suffers from high production costs, complex product separation processes, and serious environmental pollution. Biocatalysis is considered a more efficient and environment-friendly method for drug production. The cytochrome daunorubicin C-14 hydroxylase (DoxA) is the essential enzyme catalyzing the conversion of daunorubicin to doxorubicin. Herein, the DoxA from Streptomyces peucetius subsp. caesius ATCC 27952 was expressed in Escherichia coli, and the rational design strategy was further applied to improve the enzyme activity. Eight amino acid residues were identified as the key sites via molecular docking. Using a constructed screening library, we obtained the mutant DoxA(P88Y) with a more rational protein conformation, and a 56% increase in bioconversion efficiency was achieved by the mutant compared to the wild-type DoxA. Molecular dynamics simulation was applied to understand the relationship between the enzyme's structural property and its substrate-binding efficiency. It was demonstrated that the mutant DoxA(P88Y) formed a new hydrophobic interaction with the substrate daunorubicin, which might have enhanced the binding stability and thus improved the catalytic activity. Our work lays a foundation for further exploration of DoxA and facilitates the industrial process of bio-production of doxorubicin. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the steroidal saponins from the rhizomes of Paris polyohylla var. latifolia led to the discovery and characterization of three new spirostanol saponins, papolatiosides A–C (1–3), and nine known compounds (4–12). Their structures were established via extensive spectroscopic data analysis and chemical methods. Interestingly, compounds 1 and 2 possessed a fructosyl in their oligosaccharide moiety, which is rare in natural product and was firstly reported in family Melanthiaceae. The cytotoxicity of these saponins against several human cancer cell lines was evaluated by a CCK-8 experiment. As a result, compound 1 exhibited a significant cytotoxic effect on LN229, U251, Capan-2, HeLa, and HepG2 cancer cells with IC50 values of 4.18 ± 0.31, 3.85 ± 0.44, 3.26 ± 0.34, 3.30 ± 0.38 and 4.32 ± 0.51 μM, respectively. In addition, the result of flow cytometry analysis indicated that compound 1 could induce apoptosis of glioma cells LN229. The underlying mechanism was explored by network pharmacology and western bolt experiments, which indicated that compound 1 could induce glioma cells LN229 apoptosis by regulating the EGFR/PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Every year lung cancer takes the lives of many patients, making it the most common cause of cancer-related deaths. While surgery is the gold standard treatment for early-stage lung cancer, its share in treating more advanced disease stages is limited. Therefore, clinicians advise a multimodal treatment consisting of chemotherapy, radiotherapy and/or immunotherapy to treat advanced lung cancers. There has been a growing interest in loco-regional techniques as they are expected to have advantages over current therapies. In this article, we provide an overview of the established and promising innovative invasive loco-regional techniques ordered by their route of administration (endobronchial, endovascular and transthoracic route) and an overview of their implementation and effectiveness. Although the results of these techniques show improved local disease control and effect, there is a need for more clinical studies to guarantee their efficacy and safety before they can be used within the clinic. Surgical resection is still the standard treatment for early-stage lung cancer. A multimodal treatment consisting of chemotherapy, radiotherapy and/or immunotherapy is advised for more advanced disease stages (stages IIb, III and IV). The role of surgery in these stages is limited to very specific indications. Regional treatment techniques are being introduced at a high speed because of improved technology and their possible advantages over traditional surgery. This review includes an overview of established and promising innovative invasive loco-regional techniques stratified based on the route of administration, including endobronchial, endovascular and transthoracic routes, a discussion of the results for each method, and an overview of their implementation and effectiveness. [ABSTRACT FROM AUTHOR]

Sense of agency (SoA) refers to the subjective feeling of controlling one's own actions and sensory feedback. The SoA occurs when the predicted feedback matches the actual sensory feedback and is responsible for maintaining behavioral comfort. However, sensorimotor deficits because of illness cause incongruence between prediction and feedback, so the patient loses comfort during actions. Discomfort with actions associated with incongruence may continue robustly (i.e., "not" adaptable) throughout life because of the aftereffects of the disease. However, it is unclear how the SoA modulates when incongruency is experienced, even for a short term. The purpose of this study was to investigate the adaptability of the SoA in healthy participants in sensorimotor tasks for a short term. Participants were divided into congruent and incongruent exposure groups. The experimental task of manipulating the ratio of the self-control of a PC cursor was used to measure the SoA before and after exposure to congruent or incongruent stimuli. The results showed no significant differences between the groups before and after exposure for a short term. The finding that the SoA was not adaptable may assist in guiding the direction of future studies on how to correct incongruence. [ABSTRACT FROM AUTHOR]

At the first step of phage infection, the receptor-binding proteins (RBPs) such as tail fibers are responsible for recognizing specific host surface receptors. The proper folding and assembly of tail fibers usually requires a chaperone encoded by the phage genome. Despite extensive studies on phage structures, the molecular mechanism of phage tail fiber assembly remains largely unknown. Here, using a minimal myocyanophage, termed Pam3, isolated from Lake Chaohu, we demonstrate that the chaperone gp25 forms a stable complex with the tail fiber gp24 at a stoichiometry of 3:3. The 3.1-Å cryo-electron microscopy structure of this complex revealed an elongated structure with the gp25 trimer embracing the distal moieties of gp24 trimer at the center. Each gp24 subunit consists of three domains: the N-terminal α-helical domain required for docking to the baseplate, the tumor necrosis factor (TNF)-like and glycine-rich domains responsible for recognizing the host receptor. Each gp25 subunit consists of two domains: a non-conserved N-terminal β-sandwich domain that binds to the TNF-like and glycine-rich domains of the fiber, and a C-terminal α-helical domain that mediates trimerization/assembly of the fiber. Structural analysis enabled us to propose the assembly mechanism of phage tail fibers, in which the chaperone first protects the intertwined and repetitive distal moiety of each fiber subunit, further ensures the proper folding of these highly plastic structural elements, and eventually enables the formation of the trimeric fiber. These findings provide the structural basis for the design and engineering of phage fibers for biotechnological applications. [ABSTRACT FROM AUTHOR]

For the application of X80 pipelines in Northeast China, it is important to establish the correct cathodic protection (CP) potential. To achieve this, potentiodynamic polarization; electrochemical impedance spectroscopy (EIS); a slow strain rate test (SSRT); and a scanning electron microscopy (SEM) fracture morphology analysis were carried out for an X80 steel gas pipeline at several temperatures in Heilongjiang Province, China. The results show that the hydrogen evolution potential of X80 steel in soil at different temperatures was about −900 mV (vs. CSE). The generated hydrogen atoms can be adsorbed on the surface of the pipelines to reduce the surface energy, or they can be diffused into the substrate and accumulate to the critical concentration, inducing the decohesion between different structures and generating additional plastic deformation through dislocation motion. With the peak impedance potential as the minimum potential and the hydrogen embrittlement potential as the maximum potential, the CP potential of X80 steel in the soil at 30 °C, 45 °C, and 60 °C ranged from −900 mV to −1100 mV (vs. CSE), temperatures at which the X80 steel does not corrode or cause hydrogen embrittlement. [ABSTRACT FROM AUTHOR]

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (RBDCoV2) has a higher binding affinity to the human receptor angiotensin-converting enzyme 2 (ACE2) than the SARS-CoV RBD (RBDCoV). Here, we performed molecular dynamics (MD) simulations, binding free energy (BFE) calculations, and interface residue contact network (IRCN) analysis to explore the mechanistic origin of different ACE2-binding affinities of the two RBDs. The results demonstrate that, when compared to the RBDCoV2-ACE2 complex, RBDCoV-ACE2 features enhanced dynamicsand inter-protein positional movements and increased conformational entropy and conformational diversity. Although the inter-protein electrostatic attractive interactions are the primary determinant for the high ACE2-binding affinities of both RBDs, the significantly enhanced electrostatic attractive interactions between ACE2 and RBDCoV2 determine the higher ACE2-binding affinity of RBDCoV2 than of RBDCoV. Comprehensive comparative analyses of the residue BFE components and IRCNs between the two complexes reveal that it is the residue changes at the RBD interface that lead to the overall stronger inter-protein electrostatic attractive force in RBDCoV2-ACE2, which not only tightens the interface packing and suppresses the dynamics of RBDCoV2-ACE2, but also enhances the ACE2-binding affinity of RBDCoV2. Since the RBD residue changes involving gain/loss of the positively/negatively charged residues can greatly enhance the binding affinity, special attention should be paid to the SARS-CoV-2 variants carrying such mutations, particularly those near or at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2. [ABSTRACT FROM AUTHOR]

Point cloud upsampling algorithms can improve the resolution of point clouds and generate dense and uniform point clouds, and are an important image processing technology. Significant progress has been made in point cloud upsampling research in recent years. This paper provides a comprehensive survey of point cloud upsampling algorithms. We classify existing point cloud upsampling algorithms into optimization-based methods and deep learning-based methods, and analyze the advantages and limitations of different algorithms from a modular perspective. In addition, we cover some other important issues such as public datasets and performance evaluation metrics. Finally, we conclude this survey by highlighting several future research directions and open issues that should be further addressed. [ABSTRACT FROM AUTHOR]

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway. [ABSTRACT FROM AUTHOR]

Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1), (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N-norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8-methoxyisolaurenine-Noxide (5) were isolated, together with one known compound, (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks of Litsea cubeba. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and 6 showed antimicrobial activity against the bacterium S. aureus and two fungi (A. alternata and C. nicotianae). Compounds 3,4 exhibited significant cytotoxicity against all of six tested tumor cell lines. [ABSTRACT FROM AUTHOR]

Thiamine deficiency (TD) has detrimental effects on brain health and neurobehavioral development, and it is associated with many aging-related neurological disorders. To facilitate TD-related neuropsychological studies, we generated a TD mouse model by feeding a thiamine-deficient diet for 30 days, followed by re-feeding the control diet for either one week or 16 weeks as recovery treatment. We then performed neurobehavioral tests in these two cohorts: cohort of one week post TD treatment (1 wk-PTDT) and 16 weeks post TD treatment (16 wks-PTDT). The TD mice showed no significant difference from control in any tests in the 1 wk-PTDT cohort at the age of 13–14 weeks. The tests for the 16 wks-PTDT cohort at the age of 28–29 weeks, however, demonstrated anxiety and reduced locomotion in TD animals in open field and elevated plus maze. In comparison, rotor rod and water maze revealed no differences between TD and control mice. The current findings of the differential effects of the same TD treatment on locomotion and anxiety at different ages may reflect the progressive and moderate change of TD-induced neurobehavioral effects. The study suggests that, even though the immediate neurobehavioral impact of TD is modest or negligible at a young age, the impact could develop and become severe during the aging process. [ABSTRACT FROM AUTHOR]

The catalytic mechanism of Ag+ for chalcopyrite bioleaching by mesophilic culture (at 30 °C) and thermophilic culture (at 48 °C) was investigated using synchrotron radiation-based X-ray diffraction (SR-XRD) and S K-edge and Fe L-edge X-ray absorption near edge structure (XANES) spectroscopy. Bioleaching experiments showed that copper extraction from chalcopyrite bioleaching by both cultures was promoted significantly by Ag+, with more serious corrosion occurring on the minerals surface. SR-XRD and XANES analyses showed that the intermediates S0, jarosite and secondary minerals (bornite, chalcocite and covellite) formed for all bioleaching experiments. For these secondary minerals, the formation of bornite and covellite was promoted significantly in the presence of Ag+ for both cultures, while Ag+ has almost no effect on the formation of chalcocite. These results provided insight into the catalytic mechanisms of Ag+ to chalcopyrite bioleaching by the mesophilic and thermophilic cultures, which are both probably due to the rapid formation of bornite by Ag+ and the conversion of bornite to covellite. [ABSTRACT FROM AUTHOR]

The grain contamination by Aspergillus spp. has been a serious issue. This study exhibited the excellent antifungal effects of the essential oil compounds (EOCs) geraniol and citral against common grain pathogens (A. flavus and A. ochraceus) in vitro and in situ. The inhibitory mechanisms were also evaluated from the perspective of cell membrane permeability, reactive oxygen species (ROS) generation, and Aspergillus spp. growth-related gene expression. Meanwhile, the combined effects of EOCs in the vapor phase and modified atmosphere packaging (MAP) were examined to find an alternative preservation method for controlling Aspergillus spp. The results indicated that citral exhibited the antifungal activity mainly by downregulating the sporulation- and growth-related genes for both pathogens. Geraniol displayed inhibitory effectiveness against A. flavus predominantly by inducing the intracellular ROS accumulation and showed toxicity against A. ochraceus principally by changing cell membrane permeability. Furthermore, the synthetic effects of EOCs and MAP (75% CO2 and 25% N2) induced better grain quality than the current commercial fumigant AlP. These findings reveal that EOCs have potential to be a novel grain preservative for further application. [ABSTRACT FROM AUTHOR]

Androctonus australis Hector insect toxin (AaIT), an insect-selective toxin, was identified in the venom of the scorpion Androctonus australis. The exclusive and specific target of the toxin is the voltage-gated sodium channels of the insect, resulting in fast excitatory paralysis and even death. Because of its strict toxic selectivity and high bioactivity, AaIT has been widely used in experiments exploring pest bio-control. Recombinant expression of AaIT in a baculovirus or a fungus can increase their virulence to insect pests and diseases vectors. Likewise, transgenic plants expressing AaIT have notable anti-insect activity. AaIT is an efficient toxin and has great potential to be used in the development of commercial insecticides. [ABSTRACT FROM AUTHOR]

Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti. [ABSTRACT FROM AUTHOR]

The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery. [ABSTRACT FROM AUTHOR]