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Although the number of publications on formative assessment in science education has long been high, there is no bibliometric analysis or scientific mapping in the literature to understand research trends in formative assessment research. This research aimed to examine the bibliometric results of articles on formative assessment in science education. Based on the criteria for inclusion and exclusion, 94 articles were selected for analysis. The results show that between 2015-2016 and 2020-2022, the number of publications on formative assessment increased substantially. Among the top ten institutions that contributed to the research are three institutions from the United States. The results also show that the United States had the most publications. Analysis of the co-citations showed that the "Journal of Research in Science Teaching," "Science Education," and the "International Journal of Science Education" were cited more than 100 times. The three most cited studies were published in "Assessment in Education: Principles, Policy, and Practice." The results show that the researcher used formative assessment, students, science education, teaching, education, engineering education, curricula, STEM, and e-learning in research on formative assessment. In light of the obtained results, practical suggestions for further studies are made in the conclusion.

Abstract Background In the ongoing battle against BCR-ABL+ leukemia, despite significant advances with tyrosine kinase inhibitors (TKIs), the persistent challenges of drug resistance and the enduring presence of leukemic stem cells (LSCs) remain formidable barriers to achieving a cure. Methods In this study, we demonstrated that Disulfiram (DSF) induces ferroptosis to synergize with TKIs in inhibiting BCR-ABL+ cells, particularly targeting resistant cells and LSCs, using cell models, mouse models, and primary cells from patients. We elucidated the mechanism by which DSF promotes GPX4 degradation to induce ferroptosis through immunofluorescence, co-immunoprecipitation (CO-IP), RNA sequencing, lipid peroxidation assays, and rescue experiments. Results Here, we present compelling evidence elucidating the sensitivity of DSF, an USA FDA-approved drug for alcohol dependence, towards BCR-ABL+ cells. Our findings underscore DSF’s ability to selectively induce a potent cytotoxic effect on BCR-ABL+ cell lines and effectively inhibit primary BCR-ABL+ leukemia cells. Crucially, the combined treatment of DSF with TKIs selectively eradicates TKI-insensitive stem cells and resistant cells. Of particular note is DSF’s capacity to disrupt GPX4 stability, elevate the labile iron pool, and intensify lipid peroxidation, ultimately leading to ferroptotic cell death. Our investigation shows that BCR-ABL expression induces alterations in cellular iron metabolism and increases GPX4 expression. Additionally, we demonstrate the indispensability of GPX4 for LSC development and the initiation/maintenance of BCR-ABL+ leukemia. Mechanical analysis further elucidates DSF’s capacity to overcome resistance by reducing GPX4 levels through the disruption of its binding with HSPA8, thereby promoting STUB1-mediated GPX4 ubiquitination and subsequent proteasomal degradation. Furthermore, the combined treatment of DSF with TKIs effectively targets both BCR-ABL+ blast cells and drug-insensitive LSCs, conferring a significant survival advantage in mouse models. Conclusion In summary, the dual inhibition of GPX4 and BCR-ABL presents a promising therapeutic strategy to synergistically target blast cells and drug-insensitive LSCs in patients, offering potential avenues for advancing leukemia treatment.

Abstract In April and May 2023, Southeast Asia (SEA) encountered an exceptional heatwave. The Continental SEA was hardest hit, where all the countries broke their highest temperature records with measurements exceeding 42 °C, and Thailand set the region’s new record of 49 °C. This study provides a comprehensive analysis of this event by investigating its spatiotemporal evolution, physical mechanisms, forecast performance, return period, and extensive impacts. The enhanced high-pressure influenced by tropical waves, moisture deficiency and strong land-atmosphere coupling are considered as the key drivers to this extreme heatwave event. The ECMWF exhibited limited forecast skills for the reduced soil moisture and failed to capture the land-atmosphere coupling, leading to a severe underestimation of the heatwave’s intensity. Although the return period of this heatwave event is 129 years based on the rarity of temperature records, the combination of near-surface drying and soil moisture deficiency that triggered strong positive land-atmosphere feedback and rapid warming was extremely uncommon, with an occurrence probability of just 0.08%. These analyses underscore the exceptional nature of this unparalleled heatwave event and its underlying physical mechanisms, revealing its broad impacts, including significant health repercussions, a marked increase in wildfires, and diminished agricultural yields.

Biodegradable polylactic acid (PLA) melt-blown nonwovens are attractive candidates to replace non-degradable polypropylene melt-blown nonwovens. However, it is still an extremely challenging task to prepare PLA melt-blown nonwovens with sufficient mechanical properties for practical application. Herein, we report a simple strategy for the large-scale preparation of biodegradable PLA/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) melt-blown nonwovens with high strength and excellent toughness. In this process, a small amount of PHBV is added to PLA to improve the latter’s crystallization rate and crystallinity. In addition, when the PHBV content increases from 0 to 7.5 wt%, the diameters of the PLA/PHBV melt-blown fibers decrease significantly (with the proportion of nanofibers increasing from 7.7% to 42.9%). The resultant PLA/PHBV (5 wt% PHBV) melt-blown nonwovens exhibit the highest mechanical properties. The tensile stress, elongation, and toughness of PLA/PHBV (5 wt% PHBV) melt-blown nonwovens reach 2.5 MPa, 45%, and 1.0 MJ·m−3, respectively. More importantly, PLA/PHBV melt-blown nonwovens can be completely degraded into carbon dioxide and water after four months in the soil, making them environmentally friendly. A general tensile-failure model of melt-blown nonwovens is proposed in this study, which may shed light on mechanical performance enhancement for nonwovens.

Abstract Incorporating passive heating structures into personal thermal management technologies could effectively mitigate the escalating energy crisis. However, current passive heating materials struggle to balance thickness and insulating capability, resulting in compromised comfort, space efficiency, and limited thermoregulatory performance. Here, a dual air-gelation strategy, is developed to directly synthesize ultrathin and self-sustainable heating metafabric with 3D dual-network structure during electrospinning. Controlling the interactions among polymer, solvent, and water enables the microphase separation of charged jets, while adjusting the distribution of carbon black nanoparticles within charged fluids to form fibrous networks composed of interlaced aerogel micro/nanofibers with heat storage capabilities. With a low thickness of 0.18 mm, the integrated metafabric exhibits exceptional thermal insulation performance (15.8 mW m−1K−1), superhydrophobicity, enhanced mechanical properties, and high breathability while maintaining self-sustainable radiative heating ability (long-lasting warming of 8.8 °C). This strategy provides rich possibilities to develop advanced fibrous materials for smart textiles and thermal management.

Abstract RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

Abstract Late Holocene relative sea-level (RSL) data are important to understand the drivers of RSL change, but there is a lack of precise RSL records from the Sunda Shelf. Here, we produced a Late Holocene RSL reconstruction from coral microatolls in Singapore, demonstrating for the first time the utility of Diploastrea heliopora microatolls as sea-level indicators. We produced 12 sea-level index points and three marine limiting data with a precision of

The ridgetail white prawn (Exopalaemon carinicauda) belongs to the family Palaemonidae and genus Exopalaemon. Owing to its significant economic value and excellent nutritional properties, it is an important species for the development of saltwater aquaculture models in China. In this study, 160 individuals were collected from four wild populations and one artificially selected population using consolidated mitochondrial cytochrome b (mt-cyt b), and microsatellite molecular markers. The results showed that the hatcheries had lower genetic diversity than the wild samples, both at the levels of mt-cyt b (haplotype diversity: 0.123 VS 0.572; nucleotide diversity: 0.0003 VS 0.0014) and microsatellite (expected heterozygosity: 0.672 VS 0.752). Among the four wild populations, the Ningbo population sampled from the East China Sea showed higher genetic diversity in both mt-cyt b and microsatellites. A pairwise comparison of genetic differentiation coefficients revealed that the artificially selected population had not genetically diverged from the Cangzhou and Rizhao populations. However, the Ningbo population exhibited moderate to high genetic differentiation (compared to other populations), whereas the Zhanjiang population showed a high level of genetic differentiation, indicating a distinct geographical distribution pattern. Structural analysis revealed the presence of three lineage clusters in all current populations, and the artificially selected population predominantly consisted of lineage 3, accounting for 71.68 % of the population. Currently, the effective population size of hatcheries was

IntroductionEmerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women.MethodsIn this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis.ResultsThe results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene.DiscussionOur results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.

Highlights Temperature-responsive transparent nanofiber membranes were successfully fabricated using a straightforward and widely applicable method. The temperature-responsive nanofiber membranes exhibit a lower reaction temperature (~ 37 °C) and higher transmittance (> 90%). The prepared temperature-responsive transparent nanofiber membranes exhibited a short response temperature time (~ 5 s), and remarkable stability

Working stress is an important indicator reflecting the health status of structures. Passive-monitoring technology using the piezoelectric effect can effectively monitor the dynamic stress of structures. However, under static loads, the charge generated by the piezoelectric devices can only be preserved when the external circuit impedance is infinitely large, which means passive-monitoring techniques are unable to monitor static and quasi-static stress caused by slow-changing actions. In current studies, experimental observations have shown that the impedance characteristics of piezoelectric devices are affected by external static loads, yet the underlying mechanisms remain inadequately explained. This is because the impedance characteristics of piezoelectric devices are actually dynamic characteristics under alternating voltage. Most existing impedance analysis models are based on linear elastic dynamics. Within this framework, the impact of static stress on dynamic characteristics, including impedance characteristics, cannot be addressed. Accounting for static stress in impedance modeling is a challenging problem. In this study, the static stress applied on an embedded piezoelectric plate is abstracted as the initial stress of the piezoelectric plate. Based on nonlinear elastic dynamic governing equations, using the displacement method, an impedance analysis model of an embedded piezoelectric plate considering initial stress is established and verified through a fundamental experiment and a finite element analysis. Based on this, the explicit analytical relation between initial stress and impedance characterizations is provided, the mechanism of the effect of initial stress on the impedance characterizations is revealed, and procedures to identify static stress using impedance characterizations is proposed. Moreover, the sensitivities of the impedance characterizations in response to the initial stress are thoroughly discussed. This study mainly provides a theoretical basis for monitoring static stress using the electromechanical impedance of an embedded piezoelectric plate. And the results of the present study can help with the performance prediction and design optimization of piezoelectric-based static stress sensors.

Microcapsule-based self-healing cementitious composite (MSCC) offers autonomous damage repair, extending the service life of structures. However, most of the existing studies focus on static behavior and healing effectiveness but rarely explore dynamic responses. This study developed the mesoscale modeling approach to investigate MSCC behavior under dynamic split tensile loading. At the mesoscale, MSCC can be treated as a four-phase composite consisting of coarse aggregates, interfacial transition zones, cement mortar, and microcapsules. Alternatively, it can be simplified as a two-phase composite comprising a homogeneous mortar matrix and microcapsules. Four-phase and two-phase mesoscale MSCC models were developed for 2D simulations, while a two-phase 3D model was also developed for comparison. Mesoscale numerical simulations were conducted based on Split-Hopkinson Pressure Bar Brazilian disk-splitting tests, considering various strain rates. Simulation results of different mesoscale models were compared with experimental results. All of the models accurately predicted the tensile strength of MSCC, with the 2D four-phase model providing the best representation of failure modes and crack propagation. Both experimental and numerical data exhibited obvious strain rate effects, indicating that MSCC’s mechanical properties were sensitive to the loading rate. Dynamic increase factors were obtained, quantifying rate sensitivity. The obtained dynamic mechanical properties of MSCC provide insights for designing MSCC components and structures that can better withstand collisions or explosions.

In view of the common problems in power supply stations such as multiple systems, poor App experience, non linkage, and difficult data acquisition, zero code technology and robotic process automation (RPA) technology were researched, terminal service integration digital engine was built, providing zero code construction capability, order management capability, PC and mobile terminals collaboration capability, which was suitable for various disciplines such as electricity bills, metering, material, so as to realize the online, automated and mobile common service, reduce the burden and increase efficiency for the employees.

Abstract CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.

Human activities have resulted in the eutrophication of rivers, leading to heightened concerns regarding the occurrence of filamentous algal blooms. With the increasing utilization of rivers by humans, the occurrence of these nuisance filamentous algae is expected to increase in frequency in the future. Blooms primarily occur due to energy congestion at the trophic level of primary producers, resulting from inefficient energy flow in both the bottom-up and top-down pathways. To investigate the mechanism underlying the outbreak of filamentous algae, two streams in the southern Taihang catchment with different nutrient conditions were selected for this study. The objective of this study was to understand the effects of nutrient levels and other potential factors on the distribution and succession of filamentous algae. Our findings revealed a positive correlation between nutrient conditions and the biomass of filamentous algae. Cladophora and Spirogyra were identified as the dominant species among filamentous algae, each exhibiting unique distribution patterns in the two streams. Spirogyra thrived predominantly in the Baligou stream, where lower nutrient levels and warmer temperatures prevailed. In contrast, Cladophora flourished in the nutrient-rich Nanping stream at colder temperatures. Results from the generalized linear model indicated that the biomass of Cladophora was influenced by nutrient concentration, water depth, water temperature, and macrobenthic biomass. The biomass of Spirogyra, on the other hand, was primarily determined by water temperature, nutrient concentrations, water depth, and velocity. The positive correlation between Cladophora and macrobenthos revealed a possible mutually beneficial relationship, suggesting that macrobenthos may promote the growth of Cladophora by inhibiting periphytic diatoms. In return, the macrobenthos benefit from a secure refuge and an environment conducive to foraging and reproduction. This study suggested that to alleviate energy flow congestion in the benthic food chain, it is advisable to address this issue by either reducing nutrient loadings in rivers or enhancing the presence of benthivorous fishes in streams.

In the current electromechanical model of cantilevered piezoelectric energy harvesters, the assumption of uniform electric field strength within the piezoelectric layer is commonly made. This uniform electric field assumption seems reasonable since the piezoelectric layer looks like a parallel-plate capacitor. However, for a piezoelectric bender, the strain distribution along the thickness direction is not uniform, which means the internal electric field generated by the spontaneous polarization cannot be uniform. In the present study, a non-uniform electric field in the piezoelectric layer is resolved using electrostatic equilibrium equations. Based on these, the traditional distributed parameter electromechanical model is corrected and simplified to a practical single mode one. Compared with a traditional model adopting a uniform electric field, the bending stiffness term involved in the electromechanical governing equations is explicitly corrected. Through comparisons of predicted power output with two-dimensional finite element analysis, the results show that the present model can better predict the power output performance compared with the traditional model. It is found that the relative corrections to traditional model have nothing to do with the absolute dimensions of the harvesters, but only relate to three dimensionless parameters, i.e., the ratio of the elastic layer’s to the piezoelectric layer’s thickness; the ratio of the elastic modulus of the elastic layer to the piezoelectric layer; and the piezoelectric materials’ electromechanical coupling coefficient squared, k312. It is also found that the upper-limit relative corrections are only related to k312, i.e., the higher k312 is, the larger the upper-limit relative corrections will be. For a PZT-5 unimorph harvester, the relative corrections of bending stiffness and corresponding resonant frequency are up to 17.8% and 8.5%, respectively. An inverse problem to identify the material parameters based on experimentally obtained power output performance is also investigated. The results show that the accuracy of material parameters identification is improved when considering a non-uniform electric field.

Developing biodegradable polyurethane (PU) materials as an alternative to non-degradable petroleum-based PU is a crucial and challenging task. This study utilized lactide as the starting material to synthesize polylactide polyols (PLA-OH). PLA-based polyurethanes (PLA-PUs) were successfully synthesized by introducing PLA-OH into the PU molecular chain. A higher content of PLA-OH in the soft segments resulted in a substantial improvement in the mechanical attributes of the PLA-PUs. This study found that the addition of PLA-OH content significantly improved the tensile stress of the PU from 5.35 MPa to 37.15 MPa and increased the maximum elongation to 820.8%. Additionally, the modulus and toughness of the resulting PLA-PU were also significantly improved with increasing PLA-OH content. Specifically, the PLA-PU with 40% PLA-OH exhibited a high modulus of 33.45 MPa and a toughness of 147.18 MJ m−3. PLA-PU films can be degraded to carbon dioxide and water after 6 months in the soil. This highlights the potential of synthesizing PLA-PU using biomass-renewable polylactide, which is important in green and sustainable chemistry.

Abstract The Kuroshio intrusion (KI) is a northwestward‐flowing branch of the Kuroshio Current, which enters the South China Sea (SCS) and regulates its temperature, salinity, and water mass exchanges. However, limited direct observations hinder our understanding of KI's mechanisms and responses to climate change. Here, we present a 60‐year bi‐monthly resolved coral oxygen isotope (δ18Oc) record from Dongsha Atoll, the northern SCS. The dry‐season (December–March) δ18Oc record reveals interannual to decadal variabilities of the KI. The impact of the East Asian winter monsoon (EAWM) on Dongsha δ18Oc was more pronounced during the 1970s and 1980s and after the early 2000s, while the influence of the El Niño‐Southern Oscillation (ENSO) on Dongsha δ18Oc was higher between the 1980s and 1990s. The Pacific Decadal Oscillation (PDO) may have a relatively minor effect on KI strength or may indirectly modulate KI strength through its influence on ENSO activities. Our Dongsha δ18Oc record highlight the importance of the EAWM, ENSO, and PDO in predicting future KI changes.

Abstract In December 2021, Super Typhoon Rai caused significant devastation to the South Philippines and East Malaysia. In the meantime, an unprecedented flood event occurred in Peninsular Malaysia at 2,000 km west of the typhoon's path, causing comparable socioeconomic impacts as Rai. Record‐breaking 3‐day precipitation was received by Peninsular Malaysia during 16–18 December. Based on the storm tracking results, this study identified two mesoscale convective systems (MCSs) that were directly responsible for the flooding. The two MCSs were directly initiated by a tropical depression and sustained by an elongated easterly water vapor corridor originating from the Super Typhoon Rai. The return period and joint frequency analysis of key drivers indicate that the 3‐day downpour was more severe than a “once‐in‐a‐century” event. Historical records suggest such anomalous moisture channel has become more frequent in Southeast Asia, which alarms heightened attention in forecasting winter flood.

Abstract The South Atlantic Convergence Zone (SACZ) profoundly modulates precipitation from central to southeastern Brazil in the present‐day climate. However, the understanding of its long‐term behavior responding to various climate forcings remains limited. Here, we use an isotope‐enabled atmospheric general circulation model (ECHAM4.6) to examine the precipitation response of the SACZ during the mid‐Holocene about six thousand years ago. The model simulates a northward intensification of the SACZ in the mid‐Holocene, resulting in a dipole anomaly pattern relative to today's climate. The mid‐Holocene precipitation increased along the northern margin of the SACZ due to the strengthening of easterly winds across the tropical Atlantic, while an eastward deflection of the South American low‐level jet reduced moisture transport to southern Brazil, resulting in reduced precipitation along the southern margins of the SACZ. The north–south dipole response in precipitation is consistent with the mid‐Holocene hydroclimate change observed in proxy records from the region.

Cottonseed meal has been one of the predominant protein feedstuffs used in aqua feed, which contains gossypol. It is well known that gossypol, a natural polyphenolic compound found in seeds, can be toxic to fish. The toxicity of gossypol persists even after a recovery period; however, the underlying mechanism remains largely unknown. To investigate the toxic mechanism of gossypol after the recovery period, Cyprinus carpio were administered a continuous oral dose of 20 mg/kg·d gossypol (gossypol acetate dose/fish weight·d) for one week, followed by a two-week recovery period. The spleen index, spleen morphology, lysozyme (LZM) activity, acid phosphatase (ACP) activity and nitric oxide (NO) concentration were obviously changed in the spleens of C. carpio after two weeks of recovery. Then, miRNA sequencing identified 22 differentially expressed miRNAs in the spleens of C. carpio two weeks after the gossypol treatment. The mRNA expression levels of immune-associated genes were significantly increased in the spleens after recovery. MiR-194 was chosen for future study through a search of existing literature and an analysis of miRNA and mRNA expression levels. To further characterize the potential target of miR-194, we identified putative miR-194 binding sites in the 3′UTR of myeloid differentiation factor 88a (MyD88a). Dual-luciferase reporter assays revealed that miR-194 downregulated the expression level of MyD88a through binding to seed-matching sequence in the 3′ UTR of MyD88a. Moreover, C. carpio were intraperitoneally administered with miR-194 antagomir. Furthermore, down-regulation of miR-194 increased the expression levels of MyD88a and some pro-inflammatory cytokines and anti-inflammatory cytokines. Altogether, the results demonstrate miR-194 can target MyD88a to regulate the immune response of C. carpio after a two-week recovery period following gossypol administration.

Abstract Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML.

As an important mangrove species, Kandelia obovata plays an irreplaceable role in the coastal ecosystem. However, due to a lack of genetic technology, there is limited research on its functional genes. As such, establishing an efficient and rapid functional verification system is particularly important. In this study,tobacco rattle virus (TRV) and the phytoene desaturase gene KoPDS were used as the vector and target gene, respectively, to establish a virus-induced gene silencing system (VIGS) in K. obovata. Besides, the system was also used to verify the role of a Chlorophyll a/b binding protein (Cab) gene KoCAB in leaf carbon sequestration of K. obovata.RNA-Seq and qRT-PCR showed that the highest gene-silencing efficiency could reach 90% after 10 days of inoculation and maintain above 80% after 15 days, which was achieved with resuspension buffer at pH 5.8 and Agrobacterium culture at OD600 of 0.4-0.6. Taken together, the TRV-mediated VIGS system established herein is the first genetic analysis tool for mangroves, which may greatly impel functional genomics studies in mangrove plants.

Background: The epigenetic regulator in cancer progression and immune response has been demonstrated recently. However, the potential implications of 5-methylcytosine (m5C) in soft tissue sarcoma (STS) are unclear. Methods: The RNA sequence profile of 911 normal and 259 primary STS tissues were obtained from GTEx and TCGA databases, respectively. We systematically analyzed the m5C modification patterns of STS samples based on 11 m5C regulators, and comprehensively correlated these modification patterns with clinical characteristics, prognosis, and tumor microenvironment (TME) cell-infiltrating. Furthermore, an m5C-related signature was generated using Cox proportional hazard model and validated by the GSE17118 cohort. Results: Two distinct m5C modification patterns (cluster1/2) were discovered. The cluster1 had favorable overall survival, higher immune score, higher expression of most immune checkpoints, and active immune cell infiltration. The GSVA analysis of the P53 pathway, Wnt signaling pathway, G2M checkpoint, mTORC1 signaling, Wnt/β catenin signaling, and PI3K/AKT/mTOR signaling were significantly enriched in the cluster2. Moreover, 1220 genes were differentially expressed between two clusters, and a m5C prognostic signature was constructed with five m5C-related genes. The signature represented an independent prognostic factor and showed the favorable performance in the GSE17118 cohort. Patients in the low-risk group showed higher immunoscore and higher expression of most immune checkpoints. Further GSVA analysis indicated that the levels of P53 pathway, Wnt signaling pathway, and TGF-β signaling pathway were different between low- and high-risk groups. Moreover, a nomogram incorporating m5C signature and clinical variables was established and showed well performance. Conclusion: This work showed that the m5C modification plays a significant role in the progression of STS and the formation of TME diversity. Evaluating the m5C modification pattern of tumor will enhance our cognition of TME infiltration characterization to guide more effective immunotherapy strategies.

Drug combination is very common in the course of disease treatment. However, it inevitably increases the overall risk of adverse drug reactions (ADRs). It is very important to early and accurately detect and identify the potential ADRs for combined medication safety and public health. Social media is an important pharmacovigilance data source for ADR detection. But the data are complex, mass, clutter, highly sparse, so it is difficult to detect the ADR information from these data. Deep learning stands out in terms of increased accuracy. However, it takes a lot of training time and requires a lot of computing power. Quantum computing has strong parallel computing capability, and requires less computing power. By introducing attention mechanism and quantum computing into Bi-directional Long Short-Term Memory (Bi-LSTM), a quantum Bi-LSTM with attention (QBi-LSTMA) model is constructed for ADR detection from social media big data. QBi-LSTMA is composed of 6 variable component subcircuits (VQC) stacked. Under the condition that the main topology of Bi-LSTM remains unchanged, the biases of QBi-LSTMA in input gate, forgetting gate, candidate memory unit and output gate are removed to simplify the network structure, and the weight and active value qubits of the model are used to update the network weight. The performance of the proposed method is evaluated on the SMM4H dataset, comparing with one traditional ADR detection method and three deep learning based ADR detection approaches. The experiment results show that the proposed method has great potential in ADR detection.

There is a great demand for transparent films, membranes, or substrates in the fields of intelligent wearables, electronic skins, air filtration, and tissue engineering. Traditional materials such as glass and plastics cannot satisfy these requirements because of the lack of interconnected pores, undesirable porosity, and flexibility. Electrospun fibrous membranes offset these shortcomings because they contain small pores and have high porosity as well as outstanding flexibility. Thus, the development of transparent electrospun fibrous membranes is of great value. This work reports a simple and effective way to develop flexible and porous transparent fibrous membranes (TFMs) directly from electrospun fibrous membranes via mechanical pressing, without employing any other additives. In addition, the relationship between the transparency performance and the molecular structure of the polymers after pressing was summarized for the first time. After mechanical pressing, the membranes maintained fibrous morphology, micron-sized pores, and desired porosity. Polystyrene fibrous membranes, which exhibited excellent optical and mechanical properties, were used as a reference. The TFMs possessed high transparency (~89% visible light transmittance at 550 nm), high porosity (10%–30%), and strong mechanical tensile strength (~148 MPa), nearly 78 times that of the pristine electrospun fibrous membranes. Moreover, this study demonstrated that transparent and conductive membranes can be fabricated based on TFMs using vacuum-assisted filtration of silver nanowires followed by mechanical pressing. Compared with indium tin oxide films, conductive TFMs exhibited good electrical conductivities (9 Ω per square (Ω·sq−1), 78% transmittance at 550 nm) and notable mechanical performance (to bear abundant bending stresses).

New cave records from monsoon regions improve the Greenland ice core chronological framework around the Heinrich Stadial 2 by an order of magnitude, suggesting a more active role of low-latitude hydroclimate in millennial-scale climate oscillations.

Abstract Background Red ginseng (RG) was widely used as traditional Chinese medicine (TCM) or dietary supplement. However, few researches had been reported on the red ginseng polysaccharide (RGP). Methods In this study, a novel heteropolysaccharide named RGP1-1 was fractionated sequentially by DEAE-52 column and Sephadex G-100 gel column. The primary structure of RGP1-1, including glycosyl linkages, molecular weight, monosaccharide composition, morphology and physicochemical property were conducted by nuclear magnetic resonance (NMR), gas chromatography-mass spectrometer (GC–MS), atomic force microscope (AFM), scanning electron microscope (SEM), differential scanning calorimetry-thermogravimetric analysis (DSC-TG) and so on. The effect of RGP1-1 in preventing and treating myocardial ischemia was evaluated by an animal model isoprenaline (ISO) induced mice. Results RGP1-1, with a homogeneous molecular weight of 5655 Da, was composed of Glc and Gal in the ratio of 94.26:4.92. The methylation and NMR analysis indicated the backbone was composed of → 1)-Glcp-(4 → and → 1)-Galp-(4 →, branched partially at O-4 with α-D-Glcp-(1 → residue. Morphology and physicochemical property analysis revealed a triple-helical conformation, flaky and irregular spherical structure with molecule aggregations and stable thermal properties of RGP1-1. And it contained 6.82 mV zeta potential, 117.4 nm partical size and polymerization phenomenon. Furthermore, RGP1-1 possessed strong antioxidant activity in vitro and in vivo, RGP1-1 could decrease cardiomyocyte apoptosis and myocardium fibrosis of mice in histopathology and it could decrease significantly the serum levels of cardiac troponin (cTnI), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA). Western blot analysis showed that RGP1-1 can increase the expression of main protein Nuclear factor E2-related factor 2(Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1(HO-1) and kelch-like ECH-associated protein1(keap1) in oxidative stress injure progress, and therefore regulate the pathway of Nrf2/HO-1. Conclusion The above findings indicated that RGP1-1 had an improving effect on ISO-induced myocardial ischemia injury in mice, as novel natural antioxidant and heart-protecting drugs.

Cyanobacteria blooms in aquaculture ponds harm the harvesting of aquatic animals and threaten human health. Therefore, it is crucial to identify key drivers and develop methods to predict cyanobacteria blooms in aquaculture water management. In this study, we analyzed monitoring data from 331 aquaculture ponds in central China and developed two machine learning models - the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) model - to predict cyanobacterial abundance by identifying the key drivers. Simulation results demonstrated that both machine learning models are feasible for predicting cyanobacterial abundance in aquaculture ponds. The LASSO model (R2 = 0.918, MSE = 0.354) outperformed the RF model (R2 = 0.798, MSE = 0.875) in predicting cyanobacteria abundance. Farmers with well-equipped aquaculture ponds that have abundant water monitoring data can use the nine environmental variables identified by the LASSO model as an operational solution to accurately predict cyanobacteria abundance. For crude ponds with limited monitoring data, the three environmental variables identified by the RF model provide a convenient solution for useful cyanobacteria prediction. Our findings revealed that chemical oxygen demand (COD) and total organic carbon (TOC) were the two most important predictors in both models, indicating that organic carbon concentration had a close relationship with cyanobacteria growth and should be considered a key metric in water monitoring and pond management of these aquaculture ponds. We suggest that monitoring of organic carbon coupled with phosphorus reduction in feed usage can be an effective management approach for cyanobacteria prevention and to maintain a healthy ecological state in aquaculture ponds.

This work considers the effects of fiber trajectory and prepreg width on the material strength and failure behavior of variable stiffness composites. The test matrix was designed according to commonly used fiber placement trajectory and width of prepreg in engineering. Different trajectories were compared for tensile, compressive, bending, shear and CAI strengths. For tensile and compressive performance, curved ply specimens have varying degrees of decrease compared to straight ply specimens; For shear and bending performance, the optimal layup sequence is [±45/〈30|45〉]. For impact toughness, curved ply is significantly higher than straight ply, and the CAI strength of straight ply exceeds that of curved ply. For variable stiffness laminate with different fiber angles and tow widths, the maximum tensile, compressive and CAI strengths were reduced by up to 66%, 56%, and 27%, and the maximum bending strength, shear strength and impact toughness were increased by up to 53%, 23%, and 10.3%, respectively. The increase in width of prepreg leads to an increase in defects between fiber bundles which weakens the tensile/compressive performance but enhances the shear/bending performance.

Pulmonary hypertension (PH) is a refractory and fatal disease characterized by excessive pulmonary arterial cell remodeling. Uncontrolled proliferation and hypertrophy of pulmonary arterial smooth muscle cells (PASMCs), dysfunction of pulmonary arterial endothelial cells (PAECs), and abnormal perivascular infiltration of immune cells result in pulmonary arterial remodeling, followed by increased pulmonary vascular resistance and pulmonary pressure. Although various drugs targeting nitric oxide, endothelin-1 and prostacyclin pathways have been used in clinical settings, the mortality of pulmonary hypertension remains high. Multiple molecular abnormalities have been implicated in pulmonary hypertension, changes in numerous transcription factors have been identified as key regulators in pulmonary hypertension, and a role for pulmonary vascular remodeling has been highlighted. This review consolidates evidence linking transcription factors and their molecular mechanisms, from pulmonary vascular intima PAECs, vascular media PASMCs, and pulmonary arterial adventitia fibroblasts to pulmonary inflammatory cells. These findings will improve the understanding of particularly interactions between transcription factor-mediated cellular signaling pathways and identify novel therapies for pulmonary hypertension.

Abstract Traditional Chinese medicine polysaccharides (TCMPs) are plentiful and renewable resources with properties such as biocompatibility, hydrophilicity, biodegradability, and low cytotoxicity. Because the polysaccharide molecular chain contains a variety of active groups, different polysaccharide derivatives can be easily produced through chemical modification. They have been increasingly used in drug delivery systems (DDS). However, the potential of polysaccharides is usually ignored due to their structural complexity, poor stability or ambiguity of mechanisms of actions. This review summarized the applications of TCMPs in DDS around four main aspects. The general characteristics of TCMPs as drug delivery carriers, as well as the relationships between structure and function of them were summarized. Meanwhile, the direction of preparing multifunctional drug delivery materials with synergistic effect by using TCMPs was discussed. This review aims to become a reference for further research of TCMPs and their derivatives, especially applications of them as carriers in pharmaceutical preparation industry.

Crop pests seriously affect the yield and quality of crop. To timely and accurately control crop pests is particularly crucial for crop security, quality of life and a stable agricultural economy. Crop pest detection in field is an essential step to control the pests. The existing convolutional neural network (CNN) based pest detection methods are not satisfactory for small pest recognition and detection in field because the pests are various with different colors, shapes and poses. A three-scale CNN with attention (TSCNNA) model is constructed for crop pest detection by adding the channel attention and spatial mechanisms are introduced into CNN. TSCNNA can improve the interest of CNN for pest detection with different sizes under complicated background, and enlarge the receptive field of CNN, so as to improve the accuracy of pest detection. Experiments are carried out on the image set of common crop pests, and the precision is 93.16%, which is 5.1% and 3.7% higher than ICNN and VGG16, respectively. The results show that the proposed method can achieve both high speed and high accuracy of crop pest detection. This proposed method has certain practical significance of real-time crop pest control in the field.

Severe cooling at high northern latitudes, which marked the onset of Heinrich Stadial 4, was synchronous with changes in tropical monsoon systems and preceded Antarctic warming by around 300 years, according to a compilation of speleothem and ice core records.

Abstract Background The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. Methods We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. Results We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. Conclusions Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

ABSTRACT Importance The Coronavirus disease 2019 (COVID‐19) global pandemic poses a considerable challenge for pediatricians. Objective This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID‐19 in China. Methods This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results In total, 211 pediatric patients with COVID‐19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID‐19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground‐glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation Similar to adults, children of all age groups are susceptible to COVID‐19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.

Heinrich Event-3 (HE-3) differs from other Heinrich Events (HEs) in terms of the strength of its expression in climatic records from different global localities. Here, we present new high resolution δ18O records from a composite speleothem record spanning from 31.5 to 28.4 ka within the HE-3 time interval. The record is obtained from two stalagmites collected from the Thuong Thien cave (TT), northern Vietnam, which exhibit growth rates of 0.12 to 0.68 mm/yr. The TT record shows a pronounced positive excursion of δ18O values of stalagmite in the time interval from 30.8 ka and lasted about one thousand years. Specifically, the δ18O reached maximum between ∼30.3–30.2 ka and returned to low values at 29.5 ka. Both the onset and termination phases of the excursion show gradual changes in δ18O values that form a relatively symmetric ‘V’ shape. The excursion suggests that the Indian Summer Monsoon (ISM), which modulates the climate and hydrology in the region, has endured dramatic weakening in response to HE-3. The timing and duration of the monsoonal decline are consistent with a significant slowdown of the Atlantic Meridional Ocean Circulation (AMOC), which probably drove the southward migration of the intertropical convergence zone (ITCZ) and consequently a decrease in precipitation over the Asian monsoonal region including northern Vietnam. To test the proposed mechanism, we further performed modeling simulations via an atmosphere general circulation model with a coupled slab ocean. Simulated results confirm both the scale and mechanistic connections between cooling in the North Atlantic and changes in precipitation at the Thuong Thien cave locality.

Abstract Background Coronavirus disease 2019 (COVID-19) share similar symptoms with influenza A (IA), but it is more worthwhile to understand the disparities of the two infections regarding their clinical characteristics on admission. Methods A total of 71 age-matched pediatric IA and COVID-19 patient pairs were formed and their clinical data on admission were compared. Results Fever, cough, nasal congestion and nausea/vomiting were the most common symptoms on admission for both infections but occurred less often in COVID-19. The IA patients were more likely to have lower-than-normal levels of lymphocyte count and percentage and to have higher-than-normal levels of activated partial thromboplastin time, prothrombin time, serum C-reactive protein, and serum procalcitonin, while the COVID-19 patients had higher odds of having lower-than-normal levels of neutrophil count and percentage. Conclusions This study suggests that influenza A is more symptomatic than COVID-19 for children and might be an overall more severe infection at the time of admission.