Demographic dynamics and molecular evolution of the rare and endangered subsect. Gerardianae of Pinus: insights from chloroplast genomes and mitochondrial DNA markers.

MAIN CONCLUSION: The divergence of subsect. Gerardianae was likely triggered by the uplift of the Qinghai-Tibetan Plateau and adjacent mountains. Pinus bungeana might have probably experienced expansion since Last Interglacial period. Historical geological and climatic oscillations have profoundly affected patterns of nucleotide variability, evolutionary history, and species divergence in numerous plants of the Northern Hemisphere. However, how long-lived conifers responded to geological and climatic fluctuations in East Asia remain poorly understood. Here, based on paternally inherited chloroplast genomes and maternally inherited mitochondrial DNA markers, we investigated the population demographic history and molecular evolution of subsect. Gerardianae (only including three species, Pinus bungeana, P. gerardiana, and P. squamata) of Pinus. A low level of nucleotide diversity was found in P. bungeana (π was 0.00016 in chloroplast DNA sequences, and 0.00304 in mitochondrial DNAs). The haplotype-based phylogenetic topology and unimodal distributions of demographic analysis suggested that P. bungeana probably originated in the southern Qinling Mountains and experienced rapid population expansion since Last Interglacial period. Phylogenetic analysis revealed that P. gerardiana and P. squamata had closer genetic relationship. The species divergence of subsect. Gerardianae occurred about 27.18 million years ago (Mya) during the middle to late Oligocene, which was significantly associated with the uplift of the Qinghai-Tibetan Plateau and adjacent mountains from the Eocene to the mid-Pliocene. The molecular evolutionary analysis showed that two chloroplast genes (psaI and ycf1) were under positive selection, the genetic lineages of P. bungeana exhibited higher transition and nonsynonymous mutations, which were involved with the strongly environmental adaptation. These findings shed light on the population evolutionary history of white pine species and provide striking insights for comprehension of their species divergence and molecular evolution.

Design, synthesis, and biological evaluation of 2,4-diaminopyrimidine derivatives as potent Hematopoietic Progenitor Kinase 1 (HPK1) inhibitors.

HPK1 also referred to as MAP4K1, belongs to the category of mammalian STE20-like protein serine/threonine kinases. Its physiological function involves the down-regulation of T cell signals, and it is regarded as a new immune checkpoint of tumor immunology. In this study, we commenced our investigation with the hit compounds, focusing the efforts on structural optimization and SAR exploration to identify a novel class of 2,4-diaminopyrimidine HPK1 inhibitors. Notably, compound 14g exhibited a remarkable inhibitory effect on HPK1 kinase (IC50 = 0.15 nM), significantly suppressed the phosphorylation of the downstream adaptor protein SLP76 (pSLP76 IC50 = 27.92 nM), and effectively stimulated the secretion of the T cell activation marker IL-2 (EC50 = 46.64 nM). In vitro microsomal stability assay, compound 14g showed moderate stability in HLMs with T1/2 = 38.2 min and CLint = 36.4 µL·min-1·mg-1 proteins. In vivo pharmacokinetic studies, compound 14g demonstrated heightened plasma exposure (AUC0-inf = 644 ng·h·mL-1), extended half-life (T1/2 = 9.98 h), and reduced plasma clearance (CL = 52.3 mL·min-1·kg-1) compared to the reference compound after a single intravenous dose of 2 mg/kg in rats. These results indicated that compound 14g emerged as a promising inhibitor of HPK1.

Non-flooding conditions caused by water table drawdown alter microbial network complexity and decrease multifunctionality in alpine wetland soils.

Several soil functions of alpine wetland depend on microbial communities, including carbon storage and nutrient cycling, and soil microbes are highly sensitive to hydrological conditions. Wetland degradation is often accompanied by a decline in water table. With the water table drawdown, the effects of microbial network complexity on various soil functions remain insufficiently understood. In this research, we quantified soil multifunctionality of flooded and non-flooded sites in the Lalu Wetland on the Tibetan Plateau. We employed high-throughput sequencing to investigate the microbial community responses to water table depth changes, as well as the relationships between microbial network properties and soil multifunctionality. Our findings revealed a substantial reduction in soil multifunctionality at both surface and subsurface soil layers (0-20 cm and 20-40 cm) in non-flooded sites compared to flooded sites. The α-diversity of bacteria in the surface soil of non-flooded sites was significantly lower than that in flooded sites. Microbial network properties (including the number of nodes, number of edges, average degree, density, and modularity of co-occurrence networks) exhibited significant correlations with soil multifunctionality. This study underscores the adverse impact of non-flooded conditions resulting from water table drawdown on soil multifunctionality in alpine wetland soils, driven by alterations in microbial community structure. Additionally, we identified soil pH and moisture content as pivotal abiotic factors influencing soil multifunctionality, with microbial network complexity emerging as a valuable predictor of multifunctionality.

Effect of interpregnancy interval on the risk of gestational diabetes mellitus during a second pregnancy.

BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.

BINOL-Based Chiral Macrocycles and Cages.

Chirality, a fundamental principle in chemistry, biology, and medicine, is prevalent in nature and in organisms. Chiral molecules, such as DNA, RNA, and proteins, are crucial in biomolecular synthesis, as well as in the development of functional materials. Among these, 1,1'-binaphthyl-2,2'-diol (BINOL) stands out for its stable chiral configuration, versatile functionality, and commercial availability. BINOL is widely employed in asymmetric catalysis and chiral materials. This review mainly focuses on recent research over the past five years concerning the use of BINOL derivatives for constructing chiral macrocycles and cages. Their contributions to chiral luminescence, enantiomeric separation, transmembrane transport, and asymmetric catalysis were examined.

Structure-based drug design, synthesis, and biological evaluation of novel 1,3,5-triazine or pyrimidine derivatives containing benzoyl hydrazine moiety as PI3Kα selective inhibitors.

Phosphoinositide 3-kinase (PI3K) was an important cellular signal transducer, while PI3Kα was the most mutated family member in cancer. Selective PI3Kα inhibitors have become the frequent research in recent years because of their excellent curative effect and reduced side effects. Here, we described a series of PI3Kα inhibitors with 1,3,5-triazine or pyrimidine skeleton containing benzoyl hydrazine based on the pan-PI3K inhibitor ZSTK474 relying on the strategies of structure-based drug discovery (SBDD) and computer-aided drug design (CADD). Among them, compound F8 exhibited improved selective PI3Kα inhibition with an IC50 value of 0.14 nM and more significant anti-proliferative activities against three tumor-derived cell lines (PC-3 IC50 = 0.28 µM, HCT-116 IC50 = 0.57 µM, and U87-MG IC50 = 1.37 µM) than ZSTK-474. Compound F-8 induced a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells in a dose-dependent manner. Furthermore, compound F8 induced significant tumor regressions in a xenograft mouse model of U87-MG cell line with no clear evidence of toxicity following intraperitoneal injection of 40 mg/kg. Compound F8 may serve as a PI3Kα-selective inhibitor and provided the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family.

Radiographic OA, bone marrow lesions, higher body mass index and medial meniscal root tears are significantly associated with medial meniscus extrusion with OA or medial meniscal tears: a systematic review and meta-analysis.

PURPOSE: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT. METHODS: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs. RESULTS: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]. CONCLUSION: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT. LEVEL OF EVIDENCE: IV.

Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.

Determination of the Isotopic Composition of Ytterbium by MC-ICP-MS Using an Optimized Regression Model.

In this study, we measure the absolute isotope ratios of ytterbium (Yb) by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) using an optimized regression model for mass bias correction. A rhenium (Re) reference material (NIST SRM 3143), which has been characterized previously, is selected as a primary calibrator to calibrate the absolute Yb isotope ratios for three Yb materials (GSB, Alfa Yb, and GBW). The three-isotope plot for all collected data indicates that the results of Yb isotope ratios obtained are not affected by any polyatomic interferences and the mass-independent isotopic fractionation. Furthermore, the recalibrated Hf historical isotope ratios by using the absolute Yb isotopic composition obtained in this study for the isobaric interference correction on Hf isotopes are in agreement with the original historical values. This work has further demonstrated the applicability of the regression model for the calibrated measurements of absolute isotope ratios using MC-ICP-MS. The three mono-elemental Yb standard solutions are thus proposed as the reference materials for Yb isotope ratio measurements in environmental and geoscience applications.

Unveiling Latent Structure of Venture Capital Syndication Networks.

Venture capital (VC) is a form of private equity financing provided by VC institutions to startups with high growth potential due to innovative technology or novel business models but also high risks. To against uncertainties and benefit from mutual complementarity and sharing resources and information, making joint-investments with other VC institutions on the same startup are pervasive, which forms an ever-growing complex syndication network. Attaining objective classifications of VC institutions and revealing the latent structure of joint-investment behaviors between them can deepen our understanding of the VC industry and boost the healthy development of the market and economy. In this work, we devise an iterative Loubar method based on the Lorenz curve to make objective classification of VC institutions automatically, which does not require setting arbitrary thresholds and the number of categories. We further reveal distinct investment behaviors across categories, where the top-ranked group enters more industries and investment stages with a better performance. Through network embedding of joint investment relations, we unveil the existence of possible territories of top-ranked VC institutions, and the hidden structure of relations between VC institutions.

Tunable lens using dielectric elastomer sandwiched by transparent conductive liquid.

We propose and demonstrate a compact tunable lens with high transmittance using a dielectric elastomer sandwiched by transparent conductive liquid. The transparent conductive liquid not only serves as the refractive material of the tunable lens but also works as the compliant electrode of the dielectric elastomer. The overall dimensions of the proposed tunable lens are 16 mm in diameter and 10 mm in height, and the optical transmittance is as high as 92.2% at 380-760 nm. The focal power variation of the tunable lens is -23.71D at an actuation voltage of 3.0 kV. The rise and fall times are 60 ms and 185 ms, respectively. The fabrication process of the tunable lens is free of the deposition of opaque compliant electrodes. Such a tunable lens promises a potential solution in various compact imaging systems.

Dynamics of optical rogue wave generation in dispersion oscillating fibers.

We present an in-depth investigation of optical rogue waves (ORWs) during picosecond supercontinuum generations in photonic crystal fibers with periodic landscapes of group velocity dispersion and nonlinearity, namely dispersion oscillating fibers (DOFs). Specifically, it is shown via ensembles of numerical simulations that during supercontinuum generations, the rogue nature of extreme and rare events formed in uniform fibers can be effectively manipulated in DOFs. This is also verified by comparing single evolution dynamics in different dispersion longitudinal profiles. For investigating the influence of slow dynamics of ORW generation in DOFs, we increase the propagating distance and find out MI gain is still the major factor that influences the generation of ORWs. In addition, analytical results associated with simulations indicate the rogue manipulations in DOFs are attributed to the adjustable modulation-instability-gain due to periodic dispersion variation along fiber length. Finally, unlike MI in uniform fiber, MI gain side lobes result from quasi-phase-matching (QPM) relation in DOFs provide additional degree of freedom to control generations of ORWs. We believe our results will provide not only a novel insight of understanding ORW dynamics in presence of dispersion modulations, but also a new way of harnessing rogue waves in oceanology.

Resonant response and mode conversion of the microsphere coupled with a microfiber coupler.

We experimentally investigate the resonant response in a microsphere coupled with a biconical microfiber coupler (MFC) composed of single- and/or few-mode fibers. The evolution between Lorentz and Fano resonances dependent on the phase difference of the supermodes is demonstrated along the coupling region of the MFC. A flexible narrow-linewidth add-drop filter can be simultaneously achieved with the advantage of easy alignment and efficiently evanescent coupling. In addition, the mode conversion process of the microsphere is demonstrated, and the purity of the LP11 mode in a coupler at the whispering gallery mode resonance is analyzed. The proposed MFC coupling system holds great promising applications in optical filtering and sensing, mode switching, and micro-resonator-based combs.

Epigenetic Modulation on Tau Phosphorylation in Alzheimer's Disease.

Tau hyperphosphorylation is a typical pathological change in Alzheimer's disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

Ultrathin Tunable Lens Based on Boundary Tension Effect.

Solid and liquid lenses are commonly used in optical design. Such lenses have suitable thicknesses due to their working principle and processing mode. Thus, zoom optical systems comprising solid and liquid lenses are extremely large. This work presents a new ultrathin tunable lens (UTL) comprising two liquid film lenses (LFLs) obtained through aspheric deformation and produced from the surface of a micro-liquid under gravity and boundary tension. The UTL can flexibly change focal lengths between positive and negative lenses when the device thickness is merely 2.15 mm. The proposed lens has the advantages of small volume, light weight, simple fabrication, and independence from external force during zooming. This research makes up for the drawback that traditional solid and liquid lenses cannot further reduce their thicknesses. The proposed UTL provides a new lens form and fabrication method, and can be used to replace solid and liquid lenses for designing miniature zoom optical systems.

Manipulating Airy pulse in the regime of optical event horizon.

A fiber analogue of the optical event horizon is proposed via an Airy-soliton collision. The characteristics of an Airy pulse are demonstrated in a photonic crystal fiber. The robust Airy wave packet is capable of being manipulated by a strong soliton in the frame of the Airy-soliton horizon, leading to various distinctive interaction scenarios. The Airy pulse realizes the temporal reversing and still maintains its features even after undergoing a complete wavelength conversion process. Different comb-like spectra are created in the presence of Raman effect by changing the duration of the Airy pulse. The rebounds of Airy pulse in a twin-soliton trapping process is investigated. Meanwhile, a "maximally compressed" Akhmediev Breather is employed to collide with a soliton to compare with the Airy-soliton horizon case. The result can be found in the potential applications of pulse reshaping and temporal-spectral imaging for optical communication and signal processing.

Piezoelectric tuning of narrowband perfect plasmonic absorbers via an optomechanic cavity.

Optical antennas enable the control of light-matter interaction on the nanometer scale. Efficient on-chip electrical switching of plasmonic resonances is a crucial step toward the integration of optical antennas into practical optoelectronic circuits. We propose and numerically investigate the on-chip low-voltage linear electrical tuning of a narrowband optical antenna perfect absorber via a piezoelectric optomechanic cavity. Near unity absorption is realized by an array of gold nanostrip antennas separated from a membrane-based deformable backreflector by a small gap. A narrow linewidth of 33 nm at 2.58 µm is realized through the coupling between the plasmonic mode and photonic mode in the cavity-enhanced antenna structure. An aluminum nitride piezoelectric layer enabled efficient actuation of the backreflector and therefore changed the gap size, allowing for the tuning of the spectral absorption. The peak wavelength can be shifted linearly by 250 nm with 10 V of tuning voltage, and the tuning range is not limited by the pull-in effect. The polarization dependence of the nanostrip antenna coupled with the optomechanic cavity allows the use of our device as a voltage tunable polarization control device.

Design of apochromatic lens with large field and high definition for machine vision.

Precise machine vision detection for a large object at a finite working distance (WD) requires that the lens has a high resolution for a large field of view (FOV). In this case, the effect of a secondary spectrum on image quality is not negligible. According to the detection requirements, a high resolution apochromatic objective is designed and analyzed. The initial optical structure (IOS) is combined with three segments. Next, the secondary spectrum of the IOS is corrected by replacing glasses using the dispersion vector analysis method based on the Buchdahl dispersion equation. Other aberrations are optimized by the commercial optical design software ZEMAX by properly choosing the optimization function operands. The optimized optical structure (OOS) has an f-number (F/#) of 3.08, a FOV of φ60 mm, a WD of 240 mm, and a modulated transfer function (MTF) of all fields of more than 0.1 at 320 cycles/mm. The design requirements for a nonfluorite material apochromatic objective lens with a large field and high definition for machine vision detection have been achieved.

Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28.

The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7 g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7 g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7 g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7 g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer.

Humic substance mitigated the microplastic-induced inhibition of hydroxyl radical production in riparian sediment.

Hydroxyl radicals (·OH) generated during the flooding-drought transformation process play a vital role in affecting nutrient cycles at riparian zone. However, information on the processes and mechanisms for ·OH formation under the influence of microplastics (MPs) remains unclear. In this study, the effects of MPs on ·OH production from riparian sediments with different biomass [e.g., vegetation lush (VL) and vegetation barren (VB)] were studied. The results showed that presence of MPs inhibited the production of ·OH by 27 % and 7.5 % for VB and VL sediments, respectively. The inhibition was mainly resulted from the MP-induced reduction of the biotic and abiotic mediated Fe redox processes. Spectral analysis revealed that VL sediments contained more high-molecular-weight humic-like substances. Presence of MPs increased the abundances and activities of Proteobacteria, Acidobacteria and Actinobacteria, which were conducive to the changes in humification and polar properties of organic matters. The reduced humic- and fulvic-like substances were accumulated in the flooding period and substantially oxidized during flooding/drought transformation due to the enhanced MP-mediated electron transfer abilities, thus mitigated the MP-induced inhibition effects. Therefore, in order to better understanding the biogeochemical cycling of contaminants as influenced by ·OH and MPs in river ecosystems, humic substances should be considered systematically.