Genomic epidemiology reveals the variation and transmission properties of SARS-CoV-2 in a single-source community outbreak.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic, which is still a global public health concern. During March 2022, a rapid and confined single-source outbreak of SARS-CoV-2 was identified in a community in Nanjing municipal city. Overall, 95 individuals had laboratory-confirmed SARS-CoV-2 infection. The whole genomes of 61 viral samples were obtained, which were all members of the BA.2.2 lineage and clearly demonstrated the presence of one large clade, and all the infections could be traced back to the original index case. The most distant sequence from the index case presented a difference of 4 SNPs, and 118 intrahost single-nucleotide variants (iSNVs) at 74 genomic sites were identified. Some minor iSNVs can be transmitted and subsequently rapidly fixed in the viral population. The minor iSNVs transmission resulted in at least two nucleotide substitutions among all seven SNPs identified in the outbreak, generating genetically diverse populations. We estimated the overall transmission bottleneck size to be 3 using 11 convincing donor-recipient transmission pairs. Our study provides new insights into genomic epidemiology and viral transmission, revealing how iSNVs become fixed in local clusters, followed by viral transmission across the community, which contributes to population diversity.

Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.

Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.

A deep learning algorithm for the detection of aortic dissection on non-contrast-enhanced computed tomography via the identification and segmentation of the true and false lumens of the aorta.

Background: Aortic dissection is a life-threatening clinical emergency, but it is often missed and misdiagnosed due to the limitations of diagnostic technology. In this study, we developed a deep learning-based algorithm for identifying the true and false lumens in the aorta on non-contrast-enhanced computed tomography (NCE-CT) scans and to ascertain the presence of aortic dissection. Additionally, we compared the diagnostic performance of this algorithm with that of radiologists in detecting aortic dissection. Methods: We included 320 patients with suspected acute aortic syndrome from three centers (Beijing Anzhen Hospital Affiliated to Capital Medical University, Fujian Provincial Hospital, and Xiangya Hospital of Central South University) between May 2020 and May 2022 in this retrospective study. All patients underwent simultaneous NCE-CT and contrast-enhanced CT (CE-CT). The cohort comprised 160 patients with aortic dissection and 160 without aortic dissection. A deep learning algorithm, three-dimensional (3D) full-resolution U-Net, was continuously trained and refined to segment the true and false lumens of the aorta to determine the presence of aortic dissection. The algorithm's efficacy in detecting dissections was evaluated using the receiver operating characteristic (ROC) curve, including the area under the curve (AUC), sensitivity, and specificity. Furthermore, a comparative analysis of the diagnostic capabilities between our algorithm and three radiologists was conducted. Results: In diagnosing aortic dissection using NCE-CT images, the developed algorithm demonstrated an accuracy of 93.8% [95% confidence interval (CI): 89.8-98.3%], a sensitivity of 91.6% (95% CI: 86.7-95.8%), and a specificity of 95.6% (95% CI: 91.2-99.3%). In contrast, the radiologists achieved an accuracy of 88.8% (95% CI: 83.5-94.1%), a sensitivity of 90.6% (95% CI: 83.5-94.1%), and a specificity of 94.1% (95% CI: 72.9-97.6%). There was no significant difference between the algorithm's performance and radiologists' mean performance in accuracy, sensitivity, or specificity (P>0.05). Conclusions: The algorithm proficiently segments the true and false lumens in aortic NCE-CT images, exhibiting diagnostic capabilities comparable to those of radiologists in detecting aortic dissection. This suggests that the algorithm could reduce misdiagnoses in clinical practice, thereby enhancing patient care.

A Novel ANG-BSA/BCNU/ICG MNPs Integrated for Targeting Therapy of Glioblastoma.

PURPOSE: Develop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting. METHODS: Combined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors. RESULTS: ANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed. CONCLUSION: This targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.

Encapsulated mitochondria to reprogram the metabolism of M2-type macrophages for anti-tumor therapy.

M2-type macrophages (M2Φ) play a pro-tumorigenic role and are closely associated with tumor development, where metabolic dysregulation exacerbates the immunosuppressive tumor microenvironment and fosters tumor growth. Mitochondria serve as the regulatory center of cellular metabolism, yet effective methods to modulate M2Φ mitochondria within the tumor microenvironment remain lacking. In this study, we developed a technique utilizing the bio-encapsulation of mitochondria in Zeolitic Imidazolate Framework-8 (ZiF-8), referred to as Mito@ZiF-8. Our findings demonstrated that this coating protects intact mitochondria and preserves their bioactivity over an extended period after isolation. We successfully delivered Mito@ZiF-8 into M2Φ, which inhibited the secretion of pro-inflammatory factors, promoted the release of anti-inflammatory factors, and reprogrammed M2Φ metabolism. This innovative approach has the potential to reduce breast cancer cell metastasis and enhance sensitivity to chemotherapy drugs such as 6-thioguanine, cisplatin, and doxorubicin (Dox). Mito@ZiF-8 aims to reprogram the M2Φ microenvironment to support anti-tumor therapies, offering a novel strategy for improving the effectiveness of breast cancer treatment.

Enriched environment enhances angiogenesis in ischemic stroke through SDF-1/CXCR4/AKT/mTOR pathway.

Environmental-gene interactions significantly influence various bodily functions. Enriched environment (EE), a non-pharmacological treatment method, enhances angiogenesis in ischemic stroke (IS). However, underlying the role of EE in angiogenesis in aged mice post-IS remain unclear. This study aimed to determine the potential mechanism by which EE mediates angiogenesis in 12-month-old IS mice and oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells. In vivo, EE treatment alleviated the neurological deficits, enhanced angiogenesis, upregulated SDF-1, VEGFA, and the AKT/mTOR pathway. In addition, exogenous SDF-1 treatment had a protective effect similar to that of EE treatment in aged mice with IS. However, SDF-1 neutralizing antibody, AMD3100 (CXCR4 inhibitor), ARQ092 (AKT inhibitor), and rapamycin (mTOR inhibitor) treatment blocked the neuroprotective effect of EE treatment and inhibited angiogenesis in IS mice. In vitro, exogenous SDF-1 promoted migration of OGD/R-induced bEnd.3 cells and activated the AKT/mTOR pathway. AMD3100, ARQ092, and rapamycin inhibited SDF-1-induced cell migration. Collectively, these findings demonstrate that EE enhances angiogenesis and improves the IS outcomes through SDF-1/CXCR4/AKT/mTOR pathway.

Ellagic acid ameliorates alcohol-induced cognitive and social dysfunction through the gut microbiota-mediated CCL21-CCR7 axis.

Chronic alcohol consumption disrupts the balance of the gut microbiome, resulting in alcohol-induced cognitive and social dysfunction (AICSD), and serves as a primary etiological factor for early-onset dementia. Ellagic acid (EA) is a polyphenolic compound belonging to the ellagitannin family, showing potential as a dietary intervention for alleviating cognitive impairments. Nonetheless, the protective effects and underlying mechanisms of EA on AICSD remain unclear. In our study, we employed a multi-omics approach to elucidate the microbiome-mediated mechanism underlying the beneficial effects of EA on AICSD. Firstly, our findings demonstrate that EA significantly ameliorated cognitive and social behavioral deficits as well as neuroinflammation induced by alcohol. Moreover, RNA-seq analysis of hippocampi indicates that EA regulated the KEGG pathway of cytokine-cytokine receptor interaction signaling by downregulating the CCL21-CCR7 axis. Furthermore, we observed that EA effectively restored the dysbiosis of gut microbiota and their derived metabolites induced by chronic alcohol consumption. Strong connections were observed between EA-regulated genes, microbiota and metabolites. Finally, the causal relationship between the microbiome and behavioral changes was further confirmed through antibiotic treatment and fecal microbiota transplantation experiments. Overall, our study provides innovative evidence supporting the role of EA in improving AICSD via regulation of the cytokine-cytokine receptor interaction signaling pathway through the microbiota-mediated CCl21-CCR7 axis. These findings offer valuable insights into both EA-based interventions as well as microbial interventions against AICSD.

Nature of the lunar far-side samples returned by the Chang'E-6 mission.

The Chang'E-6 (CE-6) mission successfully achieved return of the first samples from the far side of the Moon. The sampling site of CE-6 is located in the South Pole-Aitken (SPA) basin-the largest, deepest and oldest impact basin on the Moon. The 1935.3 g of CE-6 lunar samples exhibit distinct characteristics compared with previous lunar samples. This study analyses the physical, mineralogical, petrographic and geochemical properties of CE-6 lunar scooped samples. The CE-6 soil has a significantly lower bulk density (0.983 g/cm3) and true density (3.035 g/cm3) than the Chang'E-5 (CE-5) samples. The grain size of the CE-6 soil exhibits a bimodal distribution, indicating a mixture of different compositions. Mineralogically, the CE-6 soil consists of 32.6% plagioclase (anorthite and bytownite), 19.7% augite, 10% pigeonite and 3.6% orthopyroxene, and with low content of olivine (0.5%) but high content of amorphous glass (29.4%). Geochemically, the bulk composition of CE-6 soil is rich in Al2O3 (14%) and CaO (12%) but low in FeO (17%), and trace elements of CE-6 soil such as K (∼630 ppm), U (0.26 ppm), Th (0.92 ppm) and rare-earth elements are significantly lower than those of the lunar soils within the Procellarum KREEP Terrane. The local basalts are characterized by low-Ti (TiO2, 5.08%), low-Al (Al2O3 9.85%) and low-K (∼830 ppm), features suggesting that the CE-6 soil is a mixture of local basalts and non-basaltic ejecta. The returned CE-6 sample contains diverse lithic fragments, including local mare basalt, breccia, agglutinate, glasses and leucocrate. These local mare basalts document the volcanic history of the lunar far side, while the non-basaltic fragments may offer critical insights into the lunar highland crust, SPA impact melts and potentially the deep lunar mantle, making these samples highly significant for scientific research.

Colloidal platinum nanoparticles enhance resin-dentin bonding durability.

OBJECTIVES: This study aims to investigate the effect of colloidal platinum nanoparticles (CPN) on the durability of resin-dentin bonding performance with contemporary adhesives. METHODS: Sixty non-carious human maxillary premolars were subjected to microtensile bond strength (µTBS) testing and divided into two main groups: CPN-treated and untreated. Within each group, specimens were randomly allocated to Clearfil Megabond 2 (MB2), Scotchbond Universal Plus Adhesive with self-etch mode (SE-SUP), and etch-and-rinse mode (ER-SUP) subgroups (n = 10/group). CPN was applied to dentin in the MB2 and SE-SUP groups for 20 s, followed by rinsing before adhesive application. In the ER-SUP group, CPN was applied after etch-and-rinse. The µTBS was tested after 24 h, 6 months, and 1 year, and the fracture modes were observed using SEM. The µTBS data were analyzed using a two-way ANOVA and post-hoc Tukey HSD test (α = 0.05). An additional twelve premolars underwent TEM/STEM/EDX for ultra-morphological observations. RESULTS: The application of CPN significantly prevented a decline in the µTBS of both the MB2 and SE-SUP groups. No significant decrease was observed in the ER-SUP group, either with aging or CPN application. Ultra-morphological images revealed platinum nanoparticles attaching to the collagen fibrils of the hybrid layer regardless of aging. It was highlighted that the nanoparticles attached to the banded collagen in the aging groups were observed. SIGNIFICANCE: CPN exhibits the potential in enhancing the longevity of resin-dentin bonding in SE mode.

Epidemiology, microbiology and antibiotic treatment of bacterial and fungal meningitis among very preterm infants in China: a cross-sectional study.

OBJECTIVE: Neonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the epidemiology of meningitis among VPIs in China. DESIGN: Cross-sectional study using the Chinese Neonatal Network database from 2019 to 2021. SETTING: 79 tertiary neonatal intensive care units in China. PATIENTS: Infants with gestational age <32 weeks or birth weight <1500 g. MAIN OUTCOME MEASURES: Incidence, pathogen distribution, antimicrobial use and outcomes of bacterial and fungal meningitis. RESULTS: Of 31 915 VPIs admitted, 122 (0.38%) infants were diagnosed with culture-confirmed meningitis, with 14 (11.5%) being early-onset (≤6 days of age) and 108 (88.5%) being late-onset (>6 days of age). The overall in-hospital mortality was 18.0% (22/122). A total of 127 pathogens were identified, among which 63.8% (81/127) were Gram-negative bacteria, 24.4% (31/127) were Gram-positive bacteria and 11.8% (15/127) were fungi. In terms of empirical therapy (on the day of the first lumbar puncture), the most commonly used antibiotic was meropenem (54.9%, 67/122). For definitive therapy (on the sixth day following the first lumbar puncture, 86 cases with available antibiotic data), meropenem (60.3%, 35/58) and vancomycin (57.1%, 16/28) were the most used antibiotics for Gram-negative and Gram-positive bacterial meningitis, respectively. 44% of infants with Gram-positive bacterial meningitis and 52% with Gram-negative bacterial meningitis received antibiotics for more than 3 weeks. CONCLUSION: 0.38% of VPIs in Chinese neonatal intensive care units were diagnosed with meningitis, experiencing significant mortality and inappropriate antibiotic therapy. Gram-negative bacteria were the predominant pathogens, with fungi emerging as a significant cause.

Trends in Venous Diameter and Brachial Artery Volume Flow of arteriovenous fistula in 12 Weeks Postoperatively.

BACKGROUND: To explore the trends of venous diameter and brachial artery volume flow (VF) in 12 weeks after arteriovenous fistula (AVF) and the influence of preoperative arterial diameter on this trend. Our goal was to clarify the maturation process within 12 weeks after AVF surgery. METHODS: Clinical data of 257 patients with end-stage renal disease who had their first radial-cephalic AVF established at our institution from February 1, 2023, to February 1, 2024, were included. The patients were divided into group A (radial artery diameter <1.5 mm), group B (radial artery diameter 1.5-2.0 mm), and group C (radial artery diameter >2.0 mm) according to the preoperative radial artery diameter. After AVF surgery, the artery and vein diameter and brachial artery VF were recorded at 1 day, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. RESULTS: The venous diameter and brachial artery VF of AVF showed an upward trend and increased significantly in 1 day-6 weeks postoperatively (P < 0.05), especially between 1 day and 2 weeks, while no significant difference in the increases at 6-12 weeks. Groups B and C were in line with the above trend, whereas the patients in group A showed best growth in 2-4 weeks postoperatively. The natural maturation rates of AVF in groups B and C were significantly better than that of group A at all postoperative time (P＜0.05). CONCLUSIONS: The AVF was in a developmentally dominant stage at 6 weeks postoperatively, with 1 day-2 weeks being particularly prominent. The postoperative natural maturation rate of AVF with arteries diameter of <1.5 mm was low; the direct use of such arteries to establish AVF needs careful consideration.

Deapi-platycodin D3 attenuates osteoarthritis development via suppression of PTP1B.

Dysregulated chondrocyte metabolism is an essential risk factor for osteoarthritis (OA) progression. Maintaining cartilage homeostasis represents a promising therapeutic strategy for the treatment of OA. However, no effective disease-modifying therapy is currently available to OA patients. To discover potential novel drugs for OA, we screened a small-molecule natural product drug library and identified deapi-platycodin D3 (D-PDD3), which was subsequently tested for its effect on extracellular matrix (ECM) properties and on OA progression. We found that D-PDD3 promoted the generation of ECM components in cultured chondrocytes and cartilage explants and that intra-articular injection of D-PDD3 delayed disease progression in a trauma-induced mouse model of OA. To uncover the underlying molecular mechanisms supporting these observed functions of D-PDD3, we explored the targets of D-PDD3 via screening approach integrating surface plasmon resonance with liquid chromatography-tandem mass spectrometry. The results suggested that D-PDD3 targeted tyrosine-protein phosphatase non-receptor type 1 (PTP1B), deletion of which restored chondrocyte homeostasis and markedly attenuated destabilization of the medial meniscus induced OA. Further cellular and molecular analyses showed that D-PDD3 maintained cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. These findings demonstrated that D-PDD3 was a potential therapeutic drug for the treatment of OA and that PTP1B served as a protein target for the development of drugs to treat OA. This study provided significant insights into the development of therapeutics for OA treatment, which, in turn, helped to improve the quality of life of OA patients and to reduce the health and economic burden.

Osteoarthritis is a degenerative disease with a high prevalence and consequently causes a burden to society. However, there is no convincing DMOAD exhibiting effective therapeutic effects on OA. In this study, we screened a small-molecule natural product drug library and identified D-PDD3, which was subsequently tested for its effect on extracellular matrix properties and on OA progression. Further cellular and in vivo experiments showed that D-PDD3 maintains cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. Our results provided fundamental evidence for applying D-PDD3-based therapies against OA, which, in turn, helps to improve the quality of life in OA patients and to reduce the health and economic burden.

Design, synthesis, and antitumor activity evaluation of 1,2,3-triazole derivatives as potent PD-1/PD-L1 inhibitors.

A series of 1,2,3-triazole derivatives targeting the PD-1/PD-L1 pathway were designed, synthesized, and evaluated both in vitro and in vivo. Among them, compound III-4 demonstrated exceptional inhibitory activity against the interaction of PD-1/PD-L1 and showed great binding affinity with hPD-L1, with an IC50 value of 2.9 nM and a KD value of 3.33 nM. In the co-culture of Hep3B/OS-8/hPD-L1 cells and CD3+ T cells assay, III-4 relieved the inhibition of PD-L1 on PD-1 and promoted the expression of IFN-γ, which shared a comparable effect to that of the PD-1 monoclonal antibody Pembrolizumab (5 µg/mL). Moreover, compound III-5, an ester prodrug derived from III-4, demonstrated significant antitumor effects in the hPD-L1-MC38 C57BL/6 mouse model (TGI: 49.6 %) by oral administration. These findings suggest that compound III-5 holds promise as an inhibitor of the PD-1/PD-L1 interaction for cancer immunotherapy.

A framework for drought monitoring and assessment from a drought propagation perspective under non-stationary environments.

According to the coupled influence of climate variation and anthropogenic activities, hydro-meteorological variables are hard to keep stationary in a changing environment. Consequently, the efficacy of traditional standardized drought indices, predicated upon the assumption of stationarity, has been called into question. In China, the challenge of drought monitoring and declaration is exacerbated by the need for multiple drought indices covering meteorological, agricultural, hydrological, and groundwater aspects, often lacking real-time availability. To address these challenges, we developed a framework for drought monitoring and assessment from a drought propagation perspective. Central to this is the Nonstationary Integrated Drought Index (NIDI), which integrates responses from meteorological, agricultural, hydrological, and groundwater droughts, accounting for climate change and anthropogenic influences. First, we analyse the process of drought propagation to select the suitable time scale standardized drought index. Subsequently, significant large-scale climatic indices are selected through linear and nonlinear correlation analyses to identify climate anomalies. Anthropogenic influences are assessed using indicators such as the Normalized Difference Vegetation Index (NDVI), Impervious Surface Ratio (ISR), and population density (POP). Nonstationary probability models are then developed for precipitation, soil moisture, runoff, and groundwater series, incorporating climatic and human-induced factors. Finally, the NIDI is calculated using a D-vine copula model, with parameter estimation and updating facilitated by a genetic algorithm, representing the temporal dependence structure among the variables. A case study in the Hulu River Basin of western China validated the NIDI. Results showed that the NIDI effectively accounts for nonstationary hydro-meteorological variables due to climate change and human activities, accurately reproducing their time-dependent structure. Compared to conventional indices like SPI, SSI, SRI, and SGI, the NIDI identifies more extreme drought events. In conclusion, the presented NIDI offers a more comprehensive approach to drought identification, providing valuable insights for accurate drought detection and effective drought-related policy-making.

A Novel Device for Micro-Droplets Generation Based on the Stepwise Membrane Emulsification Principle.

This paper presents a novel design of the device to generate microspheres or micro-droplets based on the membrane emulsification principle. Specifically, the novelty of the device lies in a proposed two-layer or stepwise (by generalization) membrane structure. An important benefit of the stepwise membrane is that it can be fabricated with the low-cost material (SU-8) and using the conventional lithography technology along with a conventional image-based alignment technique. The experiment to examine the effectiveness of the proposed membrane was conducted, and the result shows that microspheres with the size of 2.3 µm and with the size uniformity of 0.8 µm can be achieved, which meets the requirements for most applications in industries. It is noted that the traditional membrane emulsification method can only produce microspheres of around 20 µm. The main contribution of this paper is thus the new design principle of membranes (i.e., stepwise structure), which can be made by the cost-effective fabrication technique, for high performance of droplets production.

2D NiFe2O4/Ni(OH)2 Heterostructure-Based Self-Supporting Electrode With Synergistic Surface/Interfacial Engineering for Efficient Water Electrooxidation.

To meet the industrial demand for overall water splitting, oxygen evolution reaction (OER) electrocatalysts with low-cost, highly effective, and durable properties are urgently required. Herein, a facile confined strategy is utilized to construct 2D NiFe2O4/Ni(OH)2 heterostructures-based self-supporting electrode with surface-interfacial coengineering, in which abundant and ultrastable interfaces are developed. Under the high molar ratio of Ni/Fe, both spinel oxide and hydroxides phases are formed simultaneously to obtain 2D NiFe2O4/Ni(OH)2 heterostructure. The in-depth analysis indicates that the NiFe2O4/Ni(OH)2 interface displays strong electronic interactions and triggers the formation of crystalline-amorphous coexisting catalytic active NiOOH. Meanwhile, the stable catalyst-collector interface favors the electron transfer and oxygen molecules transport. The resultant 2D NiFe2O4/Ni(OH)2@CP electrode exhibits superior OER performance, including a low overpotential of 389 mV and a long operating time of 12 h at 1 A cm-2. This work paves a novel method for fabricating efficient and low-cost electrocatalysts for electrochemical conversation devices.

Genome-wide identification of R2R3-MYB transcription factors in Betula platyphylla and functional analysis of BpMYB95 in salt tolerance.

The Myeloblastosis (MYB) transcription factor (TF) family is one of the largest transcription factor families in plants and plays an important role in various physiological processes. At present, there are few reports on birch (Betula platyphylla Suk.) of R2R3-MYB-TFs, and most BpMYBs still need to be characterized. In this study, 111 R2R3-MYB-TFs with conserved R2 and R3 MYB domains were identified. Phylogenetic tree analysis showed that the MYB family members of Arabidopsis thaliana and birch were divided into 23 and 21 subgroups, respectively. The latter exhibited an uneven distribution across 14 chromosomes. There were five tandem duplication events and 17 segmental duplication events between BpMYBs, and repeat events play an important role in the expansion of the family. In addition, the promoter region of MYBs was rich in various cis-acting elements, and MYB-TFs were involved in plant growth and development, light responses, biotic stress, and abiotic stress. RNA-sequencing (RNA-seq) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results revealed that most R2R3-MYB-TFs in birch responded to salt stress. In particular, the expression of BpMYBs in the S20 subfamily was significantly induced by salt, drought, abscisic acid, and methyl jasmonate stresses. Based on the weighted co-expression network analysis of physiological and RNA-seq data of birch under salt stress, a key MYB-TF BpMYB95 (BPChr12G24087), was identified in response to salt stress, and its expression level was induced by salt stress. BpMYB95 is a nuclear localization protein with transcriptional activation activity in yeast and overexpression of this gene significantly enhanced salt tolerance in Saccharomyces cerevisiae. The qRT-PCR and histochemical staining results showed that BpMYB95 exhibited the highest expression in the roots, young leaves, and petioles of birch plants. Overexpression of BpMYB95 significantly improved salt-induced browning and wilting symptoms in birch leaves and alleviated the degree of PSII photoinhibition caused by salt stress in birch seedlings. In conclusion, most R2R3-MYB-TFs found in birch were involved in the salt stress response mechanisms. Among these, BpMYB95 was a key regulatory factor that significantly enhanced salt tolerance in birch. The findings of this study provide valuable genetic resources for the development of salt-tolerant birch varieties.

Rh(I)/Sulfoxide-Imine-Olefin Complex Catalyzed Enantioselective Allylic Alkylation of 2-Fluoromalonate: Synthesis of Chiral α-Fluorolactone Bearing Vicinal Stereogenic Centers.

Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.

Overexpression of ZlMYB1 and ZlMYB2 increases flavonoid contents and antioxidant capacity and enhances the inhibition of α-glucosidase and tyrosinase activity in rice seeds.

Anthocyanins are natural flavonoids with a high antioxidant power and many associated health benefits, but most rice produce little amounts of these compounds. In this study, 141 MYB transcription factors in 15 chromosomes, including the nucleus-localised ZlMYB1 (Zla03G003370) and ZlMYB2 (Zla15G015220), were discovered in Zizania latifolia. Overexpression of ZlMYB1 or ZlMYB2 in rice seeds induced black pericarps, and flavonoid content, antioxidant capacity, and α-glucosidase and tyrosinase inhibition effects significantly increased compared to those in the control seeds. ZlMYB1 and ZlMYB2 overexpression induced the upregulation of 764 and 279 genes, respectively, and the upregulation of 162 and 157 flavonoids, respectively, linked to a black pericarp phenotype. The expression of flavonoid 3'-hydroxylase and UDP-glycose flavonoid glycosyltransferase, as well as the activities of these enzymes, increased significantly in response to ZlMYB1 or ZlMYB2 overexpression. This study systematically confirmed that the overexpression of ZlMYB1 and ZlMYB2 promotes flavonoid biosynthesis (especially of anthocyanins) in rice.

Utilizing Macrophages Missile for Sulfate-Based Nanomedicine Delivery in Lung Cancer Therapy.

Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier-cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like "double-sided tape" to bridge metal-organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a "macrophage missile" with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a "propellant", the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.