Exotic Magnetism in Perovskite KOsO_{3}.

A new perovskite KOsO_{3} has been stabilized under high-pressure and high-temperature conditions. It is cubic at 500 K (Pm-3m) and undergoes subsequent phase transitions to tetragonal at 320 K (P4/mmm) and rhombohedral (R-3m) at 230 K as shown from refining synchrotron x-ray powder diffraction (SXRD) data. The larger orbital overlap integral and the extended wave function of 5d electrons in the perovskite KOsO_{3} allow to explore physics from the regime where Mott and Hund's rule couplings dominate to the state where the multiple interactions are on equal footing. We demonstrate an exotic magnetic ordering phase found by neutron powder diffraction along with physical properties via a suite of measurements including magnetic and transport properties, differential scanning calorimetry, and specific heat, which provide comprehensive information for a system at the crossover from localized to itinerant electronic behavior.

Males armed with big weapons win fights at limited cost in ant-mimicking jumping spiders.

A core assumption of sexual selection theory is that sexually selected weapons, specialized morphological structures used directly in male contests, can improve an individual's reproductive success but only if the bearer can overcome associated costs, the negative effects on the bearer's fitness components. However, recent studies have shown that producing and wielding exaggerated weapons may not necessarily be costly. Rather, some traits can be selected for supporting, or compensating for, the expense of producing and wielding such exaggerated weapons. In the ant-mimicking jumping spider Myrmarachne gisti, exaggerated chelicerae are borne only by adult males and not females, showing sexual dimorphism and steep positive allometry with body size. Here, we determine the potential benefits of bearing exaggerated chelicerae during male contests and explore the potential for costs in terms of prey-capture efficiency and compensation between chelicera size and neighboring trait size. While males with longer chelicerae won most of their male-male contests, we found no significant differences in prey-capture efficiency between males and females regardless of whether prey was winged or flightless. Males' elongated chelicerae thus do not impede their efficiency at capturing prey. Furthermore, we found that the sizes of all neighboring traits are positively correlated with chelicera size, suggesting that these traits may be under correlational selection. Taken together, our findings suggest that M. gisti males armed with the exaggerated chelicerae that function as weapons win more fights at limited cost for performance in prey capture and compensate for neighboring structures.

Mechanistic Studies of Iron-PyBOX-Catalyzed Olefin Amino-Oxygenation with Functionalized Hydroxylamines.

Iron-catalyzed amino-oxygenation of olefins often uses discrete ligands to increase reactivity and broaden substrate scope. This work is focused on examining ligand effects on reactivity and in situ iron speciation in a system which utilizes a bisoxazoline ligand. Freeze-trapped 57Fe Mössbauer and EPR spectroscopies as well as SC-XRD experiments were utilized to isolate and identify the species formed during the catalytic reaction of amino-oxygenation of olefins with functionalized hydroxylamines, as well as in the precatalytic mixture of iron salt and ligand. Experiments revealed significant influence of ligand and solvent on the speciation in the precatalytic mixture which led to the formation of different species which had significant influence on the reactivity. In situ experiments showed no evidence for the formation of an Fe(IV)-nitrene intermediate, and the isolation of a reactive intermediate was unsuccessful, suggesting that the use of the PyBOX ligand led to the formation of more reactive intermediates than observed in the previously studied system, preventing direct detection of intermediate species. However, isolation of the seven coordinate Fe(III) species with three carboxylate units of the hydroxylamine and spin-trap EPR experiments suggest formation of a species with unpaired electron density on the hydroxylamine nitrogen, which is in accordance with formation of a potential iron iminyl radical species, as recently proposed in literature. An observed increase in yield when substrates devoid of C-H bonds as well as isolation of a ring-closed dead-end species with substrates containing these bonds suggests the identity of the functionalized hydroxylamine can dictate the reactivity observed in these reactions.

Integration of multi-omics and clinical treatment data reveals bladder cancer therapeutic vulnerability gene combinations and prognostic risks.

Background: Bladder cancer (BCa) is a common malignancy of the urinary tract. Due to the high heterogeneity of BCa, patients have poor prognosis and treatment outcomes. Immunotherapy has changed the clinical treatment landscape for many advanced malignancies, opening new avenues for the precise treatment of malignancies. However, effective predictors and models to guide clinical treatment and predict immunotherapeutic outcomes are still lacking. Methods: We downloaded BCa sample data from The Cancer Genome Atlas to identify anti-PD-L1 immunotherapy-related genes through an immunotherapy dataset and used machine learning algorithms to build a new PD-L1 multidimensional regulatory index (PMRI) based on these genes. PMRI-related column-line graphs were constructed to provide quantitative tools for clinical practice. We analyzed the clinical characteristics, tumor immune microenvironment, chemotherapy response, and immunotherapy response of patients based on PMRI system. Further, we performed function validation of classical PMRI genes and their correlation with PD-L1 in BCa cells and screening of potential small-molecule drugs targeting PMRI core target proteins through molecular docking. Results: PMRI, which consists of four anti-PD-L1 immunotherapy-associated genes (IGF2BP3, P4HB, RAC3, and CLK2), is a reliable predictor of survival in patients with BCa and has been validated using multiple external datasets. We found higher levels of immune cell infiltration and better responses to immunotherapy and cisplatin chemotherapy in the high PMRI group than in the low PMRI group, which can also be used to predict immune efficacy in a variety of solid tumors other than BCa. Knockdown of IGF2BP3 inhibited BCa cell proliferation and migration, and IGF2BP3 was positively correlated with PD-L1 expression. We performed molecular docking prediction for each of the core proteins comprising PMRI and identified 16 small-molecule drugs with the highest affinity to the target proteins. Conclusions: Our PD-L1 multidimensional expression regulation model based on anti-PD-L1 immunotherapy-related genes can accurately assess the prognosis of patients with BCa and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical management of intermediate and advanced BCa.

Heavy Metal Pollution in Xinfengjiang River Sediment and the Response of Fish Species Abundance to Heavy Metal Concentrations.

Xinfengjiang River, the largest tributary of Dongjiang River, plays a key role in the water supply of Heyuan, Huizhou, Guangzhou and even the Pearl River urban agglomeration. It is crucial to determine the pollution status, potential ecological risk degree of heavy metals in Xinfengjiang river sediment and their influence on the abundance of fish species. In this paper, seven heavy metal concentrations in sediment from the Heyuan section of the Xinfengjiang river were investigated. The order of average concentration was: As > Zn > Pb > Cr > Cu > Cd > Hg. The average concentrations of Cd, Zn and Cu in the upper reaches of the Xinfengjiang Reservoir were significantly higher than those in the reservoir. The mean value order of Igeo was: Cd > Zn > Pb > As > Cu > Cr > Hg. Cd and As had the highest ecological risk index and the greatest threat to the ecological environment. Pearson correlation analysis and principal component analysis demonstrated that the pollution source of heavy metals such as Cu and Cd are much more likely to originate from the mine fields located in the northeast of the sampling sites. In addition, agriculture, electronic industry and domestic sewage also contributed to the concentration of heavy metals in different degrees. Redundancy analysis showed that the abundance of Cypriniformes was negatively correlated with Cu and Cd concentrations, suggesting that mining activities might indirectly affect the abundance of fish species.

Laboratory Studies on the Rheotaxis of Fish under Different Attraction Flow Conditions.

The damming of the river changes the structure of the original river ecosystem, and although fish passage plays an important role in maintaining the connectivity of the river ecosystem, the fish have difficulty finding the fish passage entrance during the upstream process. This paper studied the rheotaxis of fish under three different water flow conditions experimentally through recirculating water tanks. To better understand the response of Crucian carp (Carassius auratus) to water flow stimulation, the representative swimming trajectory, sensing success rate, attraction success rate, reaction time, and attraction time of the fish were analyzed by using a video monitoring system. The experimental results showed that fish responded differently to single-peak and lateral bimodal outflow conditions: (1) the single-peak outflow condition had a much better attraction effect than the lateral bimodal outflow condition, both in terms of sensing success rate and attraction success rate; (2) the fish swam mainly in the middle area of the lateral bimodal outflow condition, while the fish swam more evenly in the single-peak outflow condition. Therefore, setting the attraction current at the right time and near the entrance of the fish passage may help to improve the effect of fish attraction.

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure-activity relationship, and mechanisms of action (2019-2021).

Cancer, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth, remains a prominent cause of death across the world. Almost all currently available anticancer agents used in clinical practice have developed multidrug resistance, creating an urgent need to develop novel chemotherapeutics. Benzimidazole derivatives could exert anticancer properties through diverse mechanisms, inclusive of the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, antiangiogenesis, and blockage of glucose transport. Moreover, several benzimidazole-based agents have already been approved for the treatment of cancers. Hence, benzimidazole derivatives are useful scaffolds for the development of novel anticancer agents. In particular, benzimidazole hybrids could exert dual or multiple antiproliferative activities and had the potential to overcome drug resistance, demonstrating the potential of benzimidazole hybrids as potential prototypes for clinical deployment in the control and eradication of cancers. The purpose of the present review article is to provide a comprehensive landscape of benzimidazole hybrids as potential anticancer agents, and the structure-activity relationship as well as mechanisms of action are also discussed to facilitate the further rational design of more effective candidates, covering articles published from 2019 to 2021.

Cinnamic acid hybrids as anticancer agents: A mini-review.

Cancer, as a long-lasting and dramatic disease, affects almost one-third of human beings globally. Chemotherapeutics play an important role in cancer treatment, but multidrug resistance and severe adverse effects have already become the main causes of failure in tumor chemotherapy. Therefore, it is an urgent need to develop novel chemotherapeutics. Cinnamic acid contains a ubiquitous α,ß-unsaturated acid moiety presenting potential therapeutic effects in the treatment of cancer as these derivatives could act on cancer cells by diverse mechanisms of action. Accordingly, cinnamic acid derivatives are critical scaffolds in discovering novel anticancer agents. This review provides a comprehensive overview of cinnamic acid hybrids as anticancer agents. The structure-activity relationship, as well as the mechanisms of action, are also discussed, covering articles published from 2012 to 2021.

Lake ecosystem health assessment using a novel hybrid decision-making framework in the Nam Co, Qinghai-Tibet Plateau.

Lake health assessment (LHA), a powerful tool for lake ecological protection, provides the foundation for sustainable water environment management. However, existing methods have not yet considered the effects of fuzziness and randomness on LHA. In addition, most of the current studies on LHA focus on the plain areas, lack of quantitative studies in mountain areas, such as the Qinghai-Tibet Plateau. The Pythagorean fuzzy cloud (PFC) integration algorithm drawing on the advantages of Pythagorean fuzzy sets (PFS) and cloud model was proposed. A novel hybrid decision-making framework combining PFC integration algorithm and TOPSIS model was developed to determine the lake health levels with fuzziness and randomness. An indicator system incorporating ecosystem integrity (physical habitat, water quantity and quality, aquatic life) and non-ecological performance (social services) was established. To comprehensively investigate the lake health level in the Qinghai-Tibet Plateau, the Nam Co was selected as study area. Our results confirm that the developed framework in this study can overcome the shortcomings of existing methods and provide a more effective approach for LHA with fuzziness and randomness. In Nam Co, the non-ecological performance was significantly better than the ecosystem integrity. Health levels exhibited a remarkable spatial variation influenced by tourism and grazing, with decreasing health status from the northwestern to southeastern Nam Co. Approximately 85% of the sampling sites were at excellent or healthy levels, 15% were subhealthy, and no sampling sites were unhealthy and sick. Our results highlight that tourism has affected health levels at Nam Co, and effective measures are needed to minimize the impact in ecological fragile areas.

Low-cost portable bioluminescence detector based on silicon photomultiplier for on-site colony detection.

A low-cost, portable bioluminescence detector based on a silicon photomultiplier (SiPM) was developed for on-site colony detection, the main components of which are a low-noise photoelectric signal detection and processing circuit, power management module, and high-performance embedded microcontroller subsystem with peripheral circuits. Balanced chopper modulation and lock-in amplification techniques were adopted to improve the signal-to-noise ratio, and a zero-adjustment technique was used to eliminate the dark current of the SiPM to expand the dynamic range. Using this bioluminescence detector, adenosine triphosphate could be determined in the range of 3.6 × 10-6 to 3.6 × 10-11 mol/L, and bacterial colonies could be determined in the range of 1.0 × 103 to 1.0 × 109 CFU/mL, with a limit of quantitation of 1.0 × 103 CFU/mL. Satisfactory recoveries and precision were obtained. Actual samples were accurately tested and the data were verified by comparison with those from the national standard method. The manufacturing cost of the bioluminescence detector was only $30, which is only approximately 1% of the price of current commercial instruments. This study provides a tool for rapid on-site detection of bacterial colonies, as well as a new concept for the development of low-cost portable detection equipment.

A fast scan cyclic voltammetric digital circuit with precise ohmic drop compensation by online measuring solution resistance and its biosensing application.

In this work, a novel fast scan digital circuit for voltammetric analysis with precious ohmic drop compensation is developed, which is achieved through online measuring solution resistance first and then proportionally feedbacking the output signal to potentiostat's in-phase input through a potentiometer. It mainly consists of a solution resistance measurement module based on AD5933 chip, an ohmic drop automatic compensation module and a STM32F103ZET6 microcontroller. The performance of the circuit is checked successively using pure resistances, RC dummy cells, RC dummy cells incorporating a pseudo-faradaic component, and the ferrocene redox system. Results show that, precise ohmic drop compensation can be realized online and automatically, affording fast scan cyclic voltammetric (FSCV) analysis for theoretical electrochemical cells at 2000 V/s and that for practical electrochemical system using conventional electrodes at 1600 V/s. Based on this circuit, a very simple DNA biosensor for ultrasensitive detection of mercuric ions was explored. Benefitting from the high sensitivity brought by the high scan rate, the limit of quantitation (LOQ) can reach 1 pmol/L, demonstrating the application potential of FSCV in the field of ultrasensitive electrochemical detection.

Spatial distribution and convergence of provincial carbon intensity in China and its influencing factors: a spatial panel analysis from 2000 to 2017.

Unbalanced and inadequate development in China has resulted in significant temporal and spatial differences in carbon intensity, impeding the achievement of carbon reduction targets. This paper explores the spatial distribution and convergence of China's provincial carbon intensity during 2000-2017 and its influencing factors employing spatial panel techniques. The spatial distribution analysis supports the existence of significant spatial agglomeration and radiation effects in China's provincial carbon intensity, and several provinces play key roles in the spatial distribution of carbon intensity, which are an important focus of carbon emission reduction policies. The results of spatial convergence estimation support that China's provincial carbon intensity presents significant spatial absolute and conditional convergence, and after considering regional differences, the spatial convergence speed is significantly accelerated. Meanwhile, economic level, urbanization, energy consumption structure, and industrial structure have significant spatial radiation effects on carbon intensity, and carbon intensity itself also has a spatial diffusion effect, indicating that carbon emission reduction requires multi-regional coordinated actions. This paper examined the spatial distribution and convergence of China's provincial carbon intensities over 2000-2017. The empirical findings verified the spatial agglomeration and radiation effects, as well as the absolute and conditional spatial convergence of China's provincial carbon intensities, which supports the policy-making related to the carbon reduction in China.

Rapid Detection of COVID-19 by Serological Methods and the Evaluation of Diagnostic Efficacy of IgM and IgG.

BACKGROUND: In December 2019, a novel coronavirus (SARS-CoV-2) causing symptomatic illness (COVID-19) occurred in Wuhan, China. Travel-associated cases were reported in many other countries leading to epidemic transmission. The number of cases has increased rapidly but laboratory diagnosis is limited. METHODS: We collected samples from two groups of patients diagnosed with COVID-19 for experiments. In one group, 63 serum samples were analyzed IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA) and 35 healthy serum samples were served as controls. In the other group, 91 plasma samples were analyzed by colloidal gold-immunochromatographic assay (GICA) for IgG and IgM antibodies and 35 healthy plasma samples were served as controls. Throat swab samples for nucleic acids retest were collected from 81/91 of these participant. RESULTS: The sensitivity of the combined ELISA IgM and IgG detection was 55/63 (87.3%). Sensitivity of the com-bined GICA IgM and IgG detection was 75/91 (82.4%). Both methods were negative for healthy controls and had a specificity of 100%. In 81 cases, the follow up throat swab samples were retested by RT-PCR, showing that 42 cases were positive. The sensitivity was 51.9% (42/81). The area under the receiver operating characteristic (ROC) curve for IgG (AUC(IgG)) was 0.934. The area under the ROC curve for IgM (AUC(IgM)) was 0.812. The area under the ROC curve for IgG + IgM (AUC(IgG+IgM)) was 0.983. CONCLUSIONS: The serological test of SARS-CoV-2 can be used as an important supplement to the existing RT-PCR test for the specific and rapid diagnosis of COVID-19. AUC(IgG) > AUC(IgM) indicates that IgG has better classification performance than IgM. AUC(IgG + IgM) > AUC(IgG) indicates that the combination of IgG and IgM has better classification performance than IgG alone.

Diagnostic performance of culture filtered protein 10-specific perforin in pediatric patients with active tuberculosis.

BACKGROUND: Mycobacterium tuberculosis (Mtb)-specific perforin were significantly increased in patients with tuberculosis. This study aims to evaluate the diagnosis value of Mtb-specific perforin in pediatric patients with tuberculosis. METHODS: Diagnostic performance of perforin levels induced by 6-kDa early secreted antigen target (ESAT6) or culture filtered protein 10 (CFP10) were evaluated in eighty-six samples from children participants by receiver operating characteristic curve analysis. Flow cytometry was used to detect the expression of perforin and INF-γ of CD4+ , CD8+ T cells in response to CFP10 stimulation. RESULTS: After ex vivo stimulation, levels of ESAT6/CFP10-specific perforin in LTBI patients were significantly higher than active TB (ATB) patients, non-tuberculosis infection (non-TB), and health control (HC) individuals. The diagnostic efficacy of CFP10-specific perforin for TB diagnosis was significantly higher than ESAT6-specific perforin and T-SPOT assay, and when 0.74 ng/mL was taken as the cutoff value, the sensitivity, specificity, and accuracy were 97.83%, 87.5%, and 93.02%. CFP10-specific perforin in both CD4+ and CD8+ T cells were significantly higher in ATB patients compared to HCs and further increased in LTBI patients. However, INF-γ was mainly secreted by CD4+ T cells and showed no significant difference between LTBI and ATB patients. In addition, CFP10-specific perforin can effectively distinguish between ATB and LTBI with the cutoff value of 1.80 ng/mL. Sensitivity and specificity were 88.46% and 85.62%, respectively. CONCLUSIONS: CFP10-specific perforin may be used as a novel cellular immunity-based diagnostic marker of pediatric patients with tuberculosis, and with the potential for discriminating ATB from LTBI.

Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2)-infected pneumonia (COVID-19).

Objectives In December 2019, a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, China. Laboratory-based diagnostic tests utilized real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat samples. This study evaluated the diagnostic value to analyzing throat and sputum samples in order to improve accuracy and detection efficiency. Methods Paired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by the RT-PCR assay. Results The positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using the RT-PCR assay (p = 0.001). Conclusions The detection rates of 2019-nCoV from sputum specimens were significantly higher than those from throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.

Direct Intermolecular Anti-Markovnikov Hydroazidation of Unactivated Olefins.

We herein report a direct intermolecular anti-Markovnikov hydroazidation method for unactivated olefins, which is promoted by a catalytic amount of bench-stable benziodoxole at ambient temperature. This method facilitates previously difficult, direct addition of hydrazoic acid across a wide variety of unactivated olefins in both complex molecules and unfunctionalized commodity chemicals. It conveniently fills a synthetic chemistry gap of existing olefin hydroazidation procedures, and thereby provides a valuable tool for azido-group labeling in organic synthesis and chemical biology studies.

Enantioselective Synthesis of Oseltamivir Phosphate (Tamiflu) via the Iron-Catalyzed Stereoselective Olefin Diazidation.

We herein report a gram-scale, enantioselective synthesis of Tamiflu, in which the key trans-diamino moiety has been efficiently installed via an iron-catalyzed stereoselective olefin diazidation. This significantly improved, iron-catalyzed method is uniquely effective for highly functionalized yet electronically deactivated substrates that have been previously problematic. Preliminary catalyst structure-reactivity-stereoselectivity relationship studies revealed that both the iron catalyst and the complex substrate cooperatively modulate the stereoselectivity for diazidation. Safety assessment using both differential scanning calorimetry (DSC) and the drop weight test (DWT) has also demonstrated the feasibility of carrying out this iron-catalyzed olefin diazidation for large-scale Tamiflu synthesis.

Core-shell nano-latex blending method to prepare multi-shape memory polymers.

Multi-shape memory polymers were prepared by blending a series of styrene (St)-block-(styrene-random-meth acrylate (MA))-block-styrene triblock copolymer nano-latexes. These latexes synthesized using a reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization method have a core-shell structure. The cores are formed by the middle poly(St-random-MA) blocks. They act as transition phases with variable transition temperatures via adjusting the St/MA ratio. When the latexes are blended with an identical PSt shell but different poly(St-random-MA) cores, the shells play a role in preventing the aggregation of these poly(St-random-MA) cores forming a crosslinked network after hot-press treatment. Therefore a polymer with well-distributed multiple nanophases is achieved, which shows a quadruple-shape memory behavior. Furthermore, the shape memory and recovery performance at a certain temperature can be improved on purpose by increasing the mass ratio of the corresponding transition phases, which can be realized via simply varying the blending ratio of different latexes. An optimized multi-shape memory polymer with the shape memory and recovery ratio higher than 80% at all the transition temperatures is achieved.

The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity.

Multi-shape memory polymers achieved by the spatio-assembly of 3D printable thermoplastic building blocks.

Multi-shape memory polymers were prepared by the macroscale spatio-assembly of building blocks in this work. The building blocks were methyl acrylate-co-styrene (MA-co-St) copolymers, which have the St-block-(St-random-MA)-block-St tri-block chain sequence. This design ensures that their transition temperatures can be adjusted over a wide range by varying the composition of the middle block. The two St blocks at the chain ends can generate a crosslink network in the final device to achieve strong bonding force between building blocks and the shape memory capacity. Due to their thermoplastic properties, 3D printing was employed for the spatio-assembly to build devices. This method is capable of introducing many transition phases into one device and preparing complicated shapes via 3D printing. The device can perform a complex action via a series of shape changes. Besides, this method can avoid the difficult programing of a series of temporary shapes. The control of intermediate temporary shapes was realized via programing the shapes and locations of building blocks in the final device.