Search

Abstract Background It is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown. Methods The Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group. Results The hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia. Conclusion These findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.

Abstract Electrochemical carbon dioxide/carbon monoxide reduction reaction offers a promising route to synthesize fuels and value-added chemicals, unfortunately their activities and selectivities remain unsatisfactory. Here, we present a general surface molecular tuning strategy by modifying Cu2O with a molecular pyridine-derivative. The surface modified Cu2O nanocubes by 4-mercaptopyridine display a high Faradaic efficiency of greater than 60% in electrochemical carbon monoxide reduction reaction to acetate with a current density as large as 380 mA/cm2 in a liquid electrolyte flow cell. In-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy reveals stronger *CO signal with bridge configuration and stronger *OCCHO signal over modified Cu2O nanocubes by 4-mercaptopyridine than unmodified Cu2O nanocubes during electrochemical CO reduction. Density function theory calculations disclose that local molecular tuning can effectively regulate the electronic structure of copper catalyst, enhancing *CO and *CHO intermediates adsorption by the stabilization effect through hydrogen bonding, which can greatly promote asymmetric *CO-*CHO coupling in electrochemical carbon monoxide reduction reaction.

Clonal plants are widely distributed in the riparian zone and play a very important role in the maintenance of wetland ecosystem function. Flooding is an environmental stress for plants in the riparian zone, and the response of plants varies according to the depth and duration of flooding. However, there is a lack of research on the growth response of clonal plants during flooding, and the endogenous hormone response mechanism of clonal plants is still unclear. In the present study, Alternanthera philoxeroides, a clonal plant in the riparian zone, was used to investigate the time-dependent stem elongation, the elongation of different part of the immature internodes, and the relationship between growth elongation and the phytohormone gibberellin (GA) under a series of submergence depths (0 m, 2 m, 5 m, and 9 m). The results showed that stem elongation occurred under all treatments, however, compared to 0 m (control), plants grew more under 2 m and 5 m submergence depth, while grew less under 9 m water depth. Additionally, basal part elongation of the immature internode was the predominant factor contributing to the stem growth of A. philoxeroides under different submergence depths. The phytohormone contents in basal part of the mature and immature internodes showed that GA induced the differential elongation of internode. Plant submerged at depth of 2 m had the highest GA accumulation, but plant submerged at depth of 9 m had the lowest GA concentration. These data suggested that GA biosynthesis are essential for stem elongation in A. philoxeroides, and the basal part of the immature internode was the main position of the GA biosynthesis. This study provided new information about the rapid growth and invasion of the clonal plant A. philoxeroides around the world, further clarified the effects of submergence depth and duration on the elongation of the stem, and deepened our understanding of the growth response of terrestrial plants in deeply flooded environments.

Cnidarians are among the most important diploblastic organisms, elucidating many of the early stages of Metazoan evolution. However, Cnidarian fossils from Cambrian deposits have been rarely documented, mainly due to difficulties in identifying early Cnidarian representatives. Halysites, a tabulate coral from Silurian reef systems, serves as a crucial taxon for interpreting Cambrian cnidarians. Traditionally, the biological characteristics of Halysites have been analyzed using methods limited by pretreatment requirements (destructive testing) and the chamber size capacity of relevant analytical instruments. These constraints often lead to irreversible information loss and inadequate data extraction. This means that, to date, there has been no high-resolution three-dimensional mineralization analysis of Halysites. This study aims to introduce novel, non-destructive techniques to analyze the internal structure and chemical composition of Halysites. Furthermore, it seeks to elucidate the relationship between coral organisms and biomineralization in reef settings and to compare Silurian Tabulata with putative Cambrian cnidarians. Techniques such as micro-X-ray fluorescence spectrometry (micro-XRF), micro-X-ray computed tomography (micro-CT), and scanning electron microscopy (SEM) were employed in this research. With the help of high-resolution micro-CT scanning, we identify the growth pattern of Halysites, showing both lateral and vertical development. The lateral multiple-branching growth pattern of Halysites corals is first established herein. The flaggy corallite at the initial stage of branching is also observed. The micro-XRF mapping results reveal the occurrence of septa spines for Halysites, a trait previously thought rare or absent. Additionally, the ratio of coral volume to the surrounding rock was assessed, revealing that Halysites reefs were relatively sparse (volume ratio = ~30%). The cavities between Halysites likely provided more space for other organisms (e.g., rugose corals and bryozoans) when compared to other coral reef types. Additionally, we provide a comparative analysis of post-Cambrian colonial calcareous skeletons, offering insights into the structural features and growth patterns of early skeletal metazoans across the Ediacaran–Cambrian boundary.

Complete submergence, especially deep submergence, poses a serious threat to the growth and survival of plants. One study previously showed that Alternanthera philoxeroides (a herbaceous perennial plant) submerged at depth of 2 m presented fast stem elongation and reduced stem elongation as water depth increased. In the present study, we aimed to figure out from the morphological and anatomical perspective how the differential growth response of the plant to water depth was achieved. We investigated the elongation of different stem parts and the relationship of stem elongation to cell size and number in A. philoxeroides by conducting experiments using a series of submergence depths (0 m, 2 m, 5 m, and 9 m). The results showed that, in comparison with unsubmerged plants, completely submerged plants exhibited enhanced elongation at depths of 2 m and 5 m but suppressed elongation at depth of 9 m in immature stem internodes, and displayed very little elongation in mature stem internodes at any depths. The stem growth of A. philoxeroides at any submergence depth was chiefly caused by the elongation of the basal parts of immature internodes. The elongation of the basal parts of immature internodes was highly correlated to both cell proliferation and cell enlargement, but the elongation of the middle and upper parts of immature internodes correlated nearly only with cell enlargement. This study provided new information on the growth responses of A. philoxeroides to heterogeneous submergence environments and deepened our understanding of the growth performance of terrestrial plants in habitats prone to deep floods.

Abstract Optical cavities are essential for enhancing the sensitivity of molecular absorption spectroscopy, which finds widespread high-sensitivity gas sensing applications. However, the use of high-finesse cavities confines the wavelength range of operation and prevents broader applications. Here, we take a different approach to ultrasensitive molecular spectroscopy, namely dual-comb optomechanical spectroscopy (DCOS), by integrating the high-resolution multiplexing capabilities of dual-comb spectroscopy with cavity optomechanics through photoacoustic coupling. By exciting the molecules photoacoustically with dual-frequency combs and sensing the molecular-vibration-induced ultrasound waves with a cavity-coupled mechanical resonator, we measure high-resolution broadband ( > 2 THz) overtone spectra for acetylene gas and obtain a normalized noise equivalent absorption coefficient of 1.71 × 10−11 cm−1·W·Hz−1/2 with 30 GHz simultaneous spectral bandwidth. Importantly, the optomechanical resonator allows broadband dual-comb excitation. Our approach not only enriches the practical applications of the emerging cavity optomechanics technology but also offers intriguing possibilities for multi-species trace gas detection.

Abstract Cell migration is a highly orchestrated process requiring the coordination between the cytoskeleton, cell membrane and extracellular matrix adhesions. Our previous study demonstrated that Hax1 interacts with EB2, a microtubule end-binding protein, and this interaction regulate cell migration in keratinocytes. However, little is known about the underlying regulatory mechanism. Here, we show that Hax1 links dynamic focal adhesions to regulate cell migration via interacting with IQGAP1, a multidomain scaffolding protein, which was identified by affinity purification coupled with LC–MS/MS. Biochemical characterizations revealed that C-terminal region of Hax1 and RGCT domain of IQGAP1 are the most critical binding determinants for its interaction. IQGAP1/Hax1 interaction is essential for cell migration in MCF7 cells. Knockdown of HAX1 not only stabilizes focal adhesions, but also impairs the accumulation of IQGAP in focal adhesions. Further study indicates that this interaction is critical for maintaining efficient focal adhesion turnover. Perturbation of the IQGAP1/Hax1 interaction in vivo using a membrane-permeable TAT-RGCT peptide results in impaired focal adhesion turnover, thus leading to inhibition of directional cell migration. Together, our findings unravel a novel interaction between IQGAP1 and Hax1, suggesting that IQGAP1 association with Hax1 plays a significant role in focal adhesion turnover and directional cell migration. Video Abstract

Abstract While exploring the process of CO/CO2 electroreduction (COxRR) is of great significance to achieve carbon recycling, deciphering reaction mechanisms so as to further design catalytic systems able to overcome sluggish kinetics remains challenging. In this work, a model single-Co-atom catalyst with well-defined coordination structure is developed and employed as a platform to unravel the underlying reaction mechanism of COxRR. The as-prepared single-Co-atom catalyst exhibits a maximum methanol Faradaic efficiency as high as 65% at 30 mA/cm2 in a membrane electrode assembly electrolyzer, while on the contrary, the reduction pathway of CO2 to methanol is strongly decreased in CO2RR. In-situ X-ray absorption and Fourier-transform infrared spectroscopies point to a different adsorption configuration of *CO intermediate in CORR as compared to that in CO2RR, with a weaker stretching vibration of the C–O bond in the former case. Theoretical calculations further evidence the low energy barrier for the formation of a H-CoPc-CO– species, which is a critical factor in promoting the electrochemical reduction of CO to methanol.

Abstract A nonlinear finite‐time sliding mode control is proposed in this paper for the governing of complex hydroelectric systems with the finite/fixed setting time. The proposed control method is derived from the finite‐time stability and sliding mode control theories. The finite settling time is calculated and bounded, not depending on the initial conditions of the system. The solution trajectory of the controlled hydroelectric system can reach the sliding manifold in a fixed settling time, regardless of initial values. Based on the Lyapunov theory, the controlled hydroelectric system also converges to a reference state within the fixed settling time. A simulation of a high‐dimensional hydroelectric system verifies the feasibility of the proposed method. In addition, a comparison between the proposed method and the conventional PID method demonstrates the advantages of the proposed method in the shorter settling time and smaller overshoot. The proposed control method allows for the design of a flexible controller and provides an improvement in dynamic performance.

Photoacoustic spectroscopy (PAS) using two optical combs is a new-born technique, offering appealing features, including broad optical bandwidths, high resolutions, fast acquisition speeds, and wavelength-independent photoacoustic detection, for chemical sensing. However, its further application to, e.g., trace detection, is jeopardized due to the fundamentally and technically limited sensitivity and specificity. Here, we take a different route to comb-enabled PAS with acoustically enhanced sensitivity and nonlinear spectral hole-burning defined resolution. We demonstrate dual-comb quartz-enhanced PAS with two near-infrared electro-optic combs and a quartz tuning fork. Comb-line-resolved multiplexed spectra are acquired for acetylene with a single-pass detection limit at the parts-per-billion level. The technique is further extended to the mid-infrared (for methane), enabling improved sensitivity. More importantly, we measure nonlinear dual-comb photoacoustic spectra for the 12C2H2 ν1 + ν3 band P(17) transition with sub-Doppler pressure-broadening dominated homogeneous linewidths (e.g., 45.8 MHz), hence opening up new opportunities for Doppler-free photoacoustic gas sensing.

AimHypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP.MethodsA systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3.ResultsTwenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls.ConclusionThe present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022355334.

Polycystic ovary syndrome (PCOS) exerts negative effects on females of childbearing age. It is important to identify more suitable models for fundamental research on PCOS. We evaluated animal models from a novel perspective with the aim of helping researchers select the best model for PCOS. RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of mice with dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced PCOS. Meanwhile, 14 datasets were obtained from the Gene Expression Omnibus (GEO), including eight studies on humans, three on rats and three on mice, and genes associated with PCOS were obtained from the PCOSKB website. We compared the consistency of each animal model and human PCOS in terms of DEGs and pathway enrichment analysis results. There were 239 DEGs shared between prenatally androgenized (PNA) mice and PCOS patients. Moreover, 1113 genes associated with PCOS from the PCOSKB website were identified among the DEGs of PNA mice. A total of 134 GO and KEGG pathways were shared between PNA mice and PCOS patients. These findings suggest that the PNA mouse model is the best animal model to simulate PCOS.

In recent years, cities have experienced frequent climate changes and deteriorating wind environments. Urban vegetation has become an important measure to improve local microclimates with its flexible configuration. Leaves and branches also reorient with the direction of wind, affecting the airflow through the tree. However, trees are usually considered as stationary porous media areas and are not influenced by wind speed in existing numerical simulation studies. Therefore, by considering the response of a tree under natural wind, this study established a fitted relationship between porosity and wind speed by measuring the porosity of trees at different wind speeds in the field. A numerical model of the wind response of the tree was developed, and the tree drag coefficient was changed using the additional source term method to verify the feasibility of the model by measuring the wind environment behind the tree. To understand the effect of the wind-induced response on the surrounding flow field and its variation pattern, the surrounding flow fields of stationary tree (T-S) and wind-induced tree (T-D) at different wind speeds were compared and analyzed. The effect of porosity and height-to-width ratio under the wind-induced response of trees on the wind environment were quantified. It was found that at different wind speeds, as the wind speed increases, the tree porosity gradually increases and the drag coefficient decreases accordingly. The effective shading distance after wind response was 2.4H, which was 0.3H less compared to vertically fixed trees. The minimum wind speed increased linearly with plant porosity, and the minimum wind speed occurrence location and wind speed recovery distance were linearly and negatively correlated with tree height-to-width ratio. Therefore, the flow field around the tree was simulated to provide references for guiding tree planting and mitigating urban wind environments.

Global climate change has resulted in an increase in intensity and frequency of flooding, plants living in lowlands, and shore areas have to confront submergence caused by flooding, submergence-tolerant plants usually respond by adopting either escape or quiescence strategies. While certain plants exhibit a changeover from escape strategy upon partial submergence to quiescence strategy under complete shallow submergence, it remains unknown whether plants completely submerged at different water depths would adjust their strategies to cope with the change in submergence depth. Alternanthera philoxeroides is an ideal species to explore this adjustment as it is widely distributed in flood-disturbed habitats and exhibits an escape strategy when completely submerged in shallow waters. We investigated the responses of A. philoxeroides in terms of morphology, anatomy, and non-structural carbohydrate metabolism by conducting experiments using a series of submergence depths (0, 2, 5, and 9 m). During the submergence treatment, environmental factors such as light, dissolved oxygen, and temperature for submerged plants were kept constant. The results showed that A. philoxeroides plants submerged at depth of 2 m presented an escape strategy via fast stem elongation, extensive pith cavity development, and small biomass loss. However, the retarded stem elongation, reduced pith cavity transverse area, and increased biomass loss along the water depth gradient indicated that A. philoxeroides altered its growth response as water depth increased from 2 to 9 m. It is found that the changeover of response strategies occurred at higher submergence depths (5–9 m). Based on the results of our experiments, we demonstrated that water depth played an important role in driving the change in strategy. The water-depth-dependent growth performance of A. philoxeroides would benefit the species in habit exploration and exploitation. Further studies should focus on the performances of plants when submerged at varied water depths with different light climates and dissolved oxygen content, and how water depths drive the response behaviors of the submerged plants.

BackgroundOvarian cancer (OC) is one of the most lethal gynecologic malignancies and a leading cause of death in the world. Thus, this necessitates identification of prognostic biomarkers which will be helpful in its treatment.MethodsThe gene expression profiles from The Cancer Genome Atlas (TCGA) and GSE31245 were selected as the training cohort and validation cohort, respectively. The Kaplan–Meier (KM) survival analysis was used to analyze the difference in overall survival (OS) between high and low RB transcriptional corepressor 1 (RB1) expression groups. To confirm whether RB1 was an independent risk factor for OC, we constructed a multivariate Cox regression model. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were conducted to identify the functions of differentially expressed genes (DEGs). The associations of RB1 with immune infiltration and immune checkpoints were studied by the Tumor Immune Estimation Resource (TIMER 2.0) and the Gene Expression Profiling Interactive Analysis (GEPIA). The immunohistochemistry (IHC) was performed to compare the expression level of RB1 in normal tissues and tumor samples, and to predict the prognosis of OC.ResultsThe KM survival curve of the TCGA indicated that the OS in the high-risk group was lower than that in the low-risk group (HR = 1.61, 95% CI: 1.28-2.02, P = 3×10-5), which was validated in GSE31245 (HR = 4.08, 95% CI: 1.21–13.74, P = 0.01) and IHC. Multivariate Cox regression analysis revealed that RB1 was an independent prognostic biomarker (HR = 1.66, 95% CI: 1.31-2.10, P = 2.02×10-5). Enrichment analysis suggested that the DEGs were mainly involved in cell cycle, DNA replication, and mitochondrial transition. The infiltration levels of fibroblast, neutrophil, monocyte and macrophage were positively correlated with RB1. Furthermore, RB1 was associated with immune checkpoint molecules (CTLA4, LAG3, and CD274). The IHC staining revealed higher expression of RB1 in tumor tissues as compared to that in normal tissues (P = 0.019). Overexpression of RB1 was associated with poor prognosis of OC (P = 0.01).ConclusionThese findings suggest that RB1 was a novel and immune-related prognostic biomarker for OC, which may be a promising target for OC treatment.

This study was conducted to examine the effect on airflow of the shape of an urban road green belt in an asymmetrical street canyon. In this paper, the airflow field at pedestrian height in an asymmetrical street with different building height ratios (ASF) on both sides of the street is modeled and simulated using computational fluid dynamics (CFD) software, ANSYS FLUENT, and the flow rate characteristic distribution index and the average airflow intensity index are used to evaluate and analyze the airflow at the pedestrian level. The study shows that: (1) in an empty street scheme with different building ratios, the static wind area is located on the roof of the downstream building; the closer to the ground in a street with an ASF = 1/3, the lower the airflow rate. However, the situation is the opposite of that in other streets (2/3, 3/1, and 3/2). (2) The position of the green belt makes the windward side flow rate in the step-up street higher than that of the leeward side, and the flow rate of the leeward side in the step-down street is higher than that of the windward side. (3) Compared with other green belt forms, the use of two plates and three belts in the incremental street can increase the circumferential sinking at the roofs of the windward side of the street, thereby improving the wind environment in the entire street. The use of one plate, two-belt and three-plate, four-belt scenarios in the step-down street allows the two ends of the corner vortex to carry more airflow into the interior of the street and reduces both the “wind shadow effect” area in the middle of the street and the “air outlet effect” at both ends.

Hyla annectans is a tree frog living in the southwestern plateau area of China where there is strong ultraviolet radiation and long duration of sunshine. So their naked skin may possess chemical defense components that protect it from acute photo-damage. However, no such peptide or components has been identified till to date. In the current work, two novel peptides (FW-1, FWPLI-NH2 and FW-2, FWPMI-NH2) were identified from the skin of the tree frog. Five copies of FW-1 and four copies of FW-2 are encoded by an identical gene and released from the same protein precursor, which possess 167 amino acid residues. FW-1 and -2 can exert significant anti-inflammatory functions by directly inhibiting Ultraviolet B irradiation (UVB)-induced secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They may achieve this function by modulating the UV-induced stress signaling pathways such as Mitogen-activated protein kinases (MAPK) and Nuclear Factor Kappa B (NF-κB). Besides, FW-1 and -2 showed potential antioxidant effects on epidermis by attenuating the UVB-induced reactive oxygen species (ROS) production through an unknown mechanism. Considering small peptides’ easy production, storage, and potential photo-protective activity, FW-1/2 might be exciting leading compounds or templates for the development of novel pharmacological agents for the suppression of UVB-induced skin inflammation. Moreover, this study might expand our knowledge on skin defensive mechanism of tree frog upon UVB irradiation.

Constructing MOFs-composite catalyst with satisfactory catalytic efficiency as well as low cost still presents a major challenge. In this work, a low-cost modular photocatalyst with controllable activity is facilely fabricated by embedding ZIF-8 nanocrystal clusters with ammonium tetrathiomolybdate (ATTM) (donated as ZIF-MS). The embedded ATTM molecules can not only serve as photocatalytic sites but also alter the nucleation and morphology of the resulted ZIF-MS, showing controllable activity for catalytic application. Under the optimized proportion of precursors, 576.52 nm ZIF-MS nanocrystal cluster composed of 24.70 nm grain, showing high activity and size selectivity for the photocatalytic degradation of environmental pollutants, was obtained. The combination of size-selectivity of structure-tunable ZIFs with high photocatalytic activity of embedded noble-free inorganic photocatalytic agent makes these ZIF-MS ideal candidates for photocatalytic applications. Keywords: Ammonium tetrathiomolybdate, MOFs, Photocatalysis, Controllable catalyst, Size-selectivity

We propose and experimentally demonstrate single-pixel photon counting imaging based on dual-comb interferometry at 1550 nm. Different from traditional dual-comb imaging, this approach enables imaging at the photon-counting regime by using single-photon detectors combined with a time-correlated single-photon counter to record the returning photons. The illumination power is as low as 14 pW, corresponding to 2.2 × 10−3 photons/pulse. The lateral resolution is about 50 μm. This technique paves the way for applying dual-comb in remote sensing and imaging.