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Abstract Fullerene derivatives are extensively employed in inverted perovskite solar cells due to their excellent electron extraction capabilities. However, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) agglomerates easily in solution and exhibits a relatively low ionization barrier, increasing charge recombination losses and charge accumulation in the interface. Here, tetramethylthiuram disulfide (TMDS) is introduced into the PCBM solution to induce the formation of reducing sulfur radicals through UV light irradiation, allowing for n doping of the PCBM material. The resulting modified PCBM layer exhibits enhanced conductivity and electron mobility, significantly suppressing charge recombination. As a result, the resulting devices incorporating TMDS achieve a champion efficiency of 26.10% (certified 25.39%) and 24.06% at a larger area (1.0 cm2) with negligible hysteresis. More importantly, the optimized devices retain 95% and 90% of their initial efficiency after 1090 h under damp heat testing (85 °C and 85% relative humidity) and after 1271 h under maximum power point-tracking conditions, respectively.

Primula medogensis W.B Ju, B. Xu & X.F. Gao 2023, a new species categorized under P. sect. Cordifoliae, was officially described in 2023. Given its recent classification, the genetic resources for this species are currently very limited. Here, we sequenced and assembled the first complete chloroplast genome of P. medogensis using Illumina sequencing technology. The complete chloroplast genome of P. medogensis is 151,486 bp in length, exhibiting a typical quadripartite structure. It consists of a large single-copy region (LSC; 83,407 bp) and a small single-copy region (SSC;17675 bp), separated by a pair of inverted repeat regions (IRs; 25202 bp). A total of 131 genes were annotated, including 86 protein-coding, 37 tRNA, and eight rRNA genes. The overall GC content was 37.1%. Phylogenetic analysis of 59 Primula species revealed a close relationship between P. medogensis and P. calliantha subsp. bryophila.

Abstract The original load control model of microgrid based on demand response lacks the factors of incentive demand response, the overall satisfaction of users is low, the degree of demand response is low, the Time Of Use (TOU) price of peak-valley filling capacity is weak, and the peak-valley difference of load curve is large. Regarding the limitations of the current microgrid demand response model, this study further optimizes the flexible load control strategy and proposes a two-objective optimization model based on price and incentive. Meanwhile, the model is solved using an improved chaotic particle group algorithm. Finally, the microgrid load data were selected for simulation analysis. The simulation results showed that the comprehensive demand response of flexible control model proposed increased the overall satisfaction of users by 9.51%, the overall operating cost of microgrid suppliers decreased by 12.975/ten thousand yuan, the peak valley difference decreased by 4.61%, and the user demand response increased by 27.24%. The model effectively improves the overall profit of the supply side of the microgrid, improves the user satisfaction, and maximizes the linkage benefits of the supply and demand of the micro grid. In addition, the model effectively reduces the phenomenon of distributed power supply in the microgrid, and realizes the supply and demand matching of the whole load in the microgrid.

Polygala qii, a new species, is described and illustrated from limestone landform in southern Hunan, China. The new species resembles P. fallax and P. arillata in flower structure of the plants, but readily differs from the latter two in having erect and shorter inflorescences (0.2–1cm VS 10–15cm VS 7–10cm), and fewer flowers (1–5 flowers VS 10–30 flowers VS 10–20 flowers), and the latter two have a later flowering period (late March to mid-April VS May to August VS May to October). And it is an extremely unique new species that will hibernate in the hot summer of July and August. Following the IUCN Red List Criteria, P. qii is assessed as ‘Data Deficient (DD)’.

Catenary optics enables metasurfaces with higher efficiency and wider bandwidth, and is highly anticipated in the imaging system, super-resolution lithography, and broadband absorbers. However, the periodic boundary approximation without considering aperiodic electromagnetic crosstalk poses challenges for catenary optical devices to reach their performance limits. Here, perfect control of both local geometric and propagation phases is realized through field-driven optimization, in which the field distribution is calculated under real boundary conditions. Different from other optimization methods requiring a mass of iterations, the proposed design method requires less than ten iterations to get the efficiency close to the optimal value. Based on the library of shape-optimized catenary structures, centimeter-scale devices can be designed in ten seconds, with the performance improved by ~15%. Furthermore, this method has the ability to extend catenary-like continuous structures to arbitrary polarization, including both linear and elliptical polarizations, which is difficult to achieve with traditional design methods. It provides a way for the development of catenary optics and serves as a potent tool for constructing high-performance optical devices.

Abstract The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.

Background In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses.Methods To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme−/− ID8 tumor cells into C57BL/6 mice.Results Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1–caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model.Conclusions PARPis induce a specific type of ICD called pyroptosis via TNF–caspase 8–GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions.Trial registration number NCT04507841.

BackgroundLong-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle.MethodsThe cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8 g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis.ResultsHepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle.ConclusionThese findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

Abstract UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.

Wide-angle imaging and spectral detection play vital roles in tasks such as target tracking, object classification, and anti-camouflage. However, limited by their intrinsically different architectures, as determined by frequency dispersion requirements, their simultaneous implementation in a shared-aperture system is difficult. Here, we propose a novel concept to realize reconfigurable dual-mode detection based on electrical-control tunable metasurfaces. As a proof-of-concept demonstration, the simultaneous implementation of wide-angle imaging and polarization-spectral detection in a miniature shared-aperture meta-optical system is realized for the first time via the electrical control of cascaded catenary-like metasurfaces. The proposed system supports the imaging (spectral) resolution of approximately 27.8 line-pairs per millimeter (lp·mm−1; ∼80 nm) for an imaging (spectral) mode from 8 to 14 μm. This system also bears a large field of view of about 70°, enabling multi-target recognition in both modes. This work may promote the miniaturization of multifunctional optical systems, including spectrometers and polarization imagers, and illustrates the potential industrial applications of meta-optics in biomedicine, security, space exploration, and more.

Due to the complex marine environment, ship engines are under the harsh working conditions of high humidity and high salinity for a long time, which seriously aggravates the frictional wear of engine chains and thus affects the working stability and the fatigue life of engines. Based on this, this study designs the surface textures on the chain pin in three shapes—square, sine and circular. Combining experiments and simulations, the influence of texture shape, area occupancy and depth on the friction and wear resistance is studied in order to provide new ideas and theoretical basis for solving the long-term engine chain wear problem. The results show that the presence of the texture reduces the elemental Cr content of the surface after wear and thus improves the surface wear resistance compared to a smooth no-texture surface. Among the three texture shapes, the sinusoidal texture exhibites the best friction reduction and wear resistance performance, and the highest friction reduction rate of about 31. 9% is achieved under high speed and light load conditions. The sinusoidal texture has the shallowest surface wear marks, and the wear process is mainly micro-motion wear, accompanied by slight adhesive wear.

Abstract Halogenation of Y‐series small‐molecule acceptors (Y‐SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power‐conversion‐efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D‐structured large π‐fused core of guest Y‐SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D‐conjugated Y‐SMAs (X‐QTP‐4F, including halogen‐free H‐QTP‐4F, chlorinated Cl‐QTP‐4F, brominated Br‐QTP‐4F, and iodinated I‐QTP‐4F) by attaching different halogens into 2D‐conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X‐QTP‐4F, Cl‐QTP‐4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8‐BO host. Moreover, among ternary PM6:L8‐BO:X‐QTP‐4F blends, PM6:L8‐BO:Cl‐QTP‐4F obtains a more uniform and size‐suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8‐BO:Cl‐QTP‐4F‐based OSCs achieve a 19.0% efficiency, which is among the state‐of‐the‐art OSCs based on 2D‐conjugated Y‐SMAs and superior to these devices based on PM6:L8‐BO host (17.70%) and with guests of H‐QTP‐4F (18.23%), Br‐QTP‐4F (18.39%), and I‐QTP‐4F (17.62%). The work indicates that halogenation in 2D‐structured dibenzo[f,h]quinoxaline core of Y‐SMAs guests is a promising strategy to gain efficient ternary OSCs.

Abstract Epigenetic modulation is well established in hematologic malignancies but to a lesser degree in solid tumors. Here we report the results of a phase Ib/II study of guadecitabine and durvalumab in advanced clear cell renal cell carcinoma (ccRCC; NCT03308396). Patients received guadecitabine (starting at 60 mg/m2 subcutaneously on days 1-5 with de-escalation to 45 mg/m2 in case of dose limiting toxicity) with durvalumab (1500 mg intravenously on day 8). The study enrolled 57 patients, 6 in phase Ib with safety being the primary objective and 51in phase II, comprising 2 cohorts: 36 patients in Cohort 1 were treatment naive to checkpoint inhibitors (CPI) with 0-1 prior therapies and 15 patients in Cohort 2 were treated with up to two prior systemic therapies including one CPI. The combination of guadecitabine 45 mg/m2 with durvalumab 1500 mg was deemed safe. The primary objective of overall response rate (ORR) in cohort 1 was 22%. Sixteen patients (44%) experienced stable disease (SD). Secondary objectives included overall survival (OS), duration of response, progression-free survival (PFS), clinical benefit rate, and safety as well as ORR for Cohort 2. Median PFS for cohort 1 and cohort 2 were 14.26 and 3.91 months respectively. Median OS was not reached. In cohort 2, one patient achieved a partial response and 60% achieved SD. Asymptomatic neutropenia was the most common adverse event. Even though the trial did not meet the primary objective in cohort 1, the tolerability and PFS signal in CPI naive patients are worth further investigation.

Objective To compare the current standards and explore the influencing factors for hemolysis rate of leukocyte-reduced red blood cells at the end of the preservation period, in order to formulate reasonable internal control indicators. Methods A retrospective analysis was performed on hemolysis rate of 427 samples of leukocyte-reduced red blood cells at the end of the preservation period in Nanning Blood Center from 2015 to 2022. Compared with the current standard for hemolysis rate at the end of the preservation period (GB 18469-2012 Quality Requirements for Whole Blood and Component Blood), the differences were analyzed, and the factors influncing the hemolysis rate were analyzed in terms of different blood donor groups. Results 1) Among the 427 samples, the hemolysis rate of 418 (97.89%) did not exceed 0.4%, all lower than 0.8%; 2)the hemolysis rate of the male group was higher than that of the female group; 3) the hemolysis rate of the 18-29 years old group was lower than that of the 30-39 year old group and the 40-60 year old group, with statistically significant difference; 4) in terms of occupation, the hemolysis rate of students was the lowest, and the differences between groups were statistically significant; 5) no statistical significance was found in ethnicity and blood type. Conclusion Statistics indicated that gender, age, blood donation volume and occupation of blood donors were the influencing factors of hemolysis rate. The current standard is obviously higher in the qualified range of blood quality control in Nanning. It is advisable to formulate a reasonable quality control strategy with internal control index of hemolysis rate set

Photonic integrated circuits (PICs) have attracted significant interest in communication, computation, and biomedical applications. However, most rely on highly integrated PICs devices, which require a low-loss and high-integration guided wave path. Owing to the various dimensions of different integrated photonic devices, their interconnections typically require waveguide tapers. Although a waveguide taper can overcome the width mismatch of different devices, its inherent tapering width typically results in a long length, which fundamentally limits the efficient interconnection between devices with a high scaling ratio over a short distance. Herein, we proposed a highly integrated on-chip metalens that enables optical interconnections between devices with high width-scaling ratios by embedding a free-form metasurface in a silicon-on-insulator film. The special geometric features endow the designed metalens with high coupling efficiency and high integration. The device has a footprint of only 2.35 μm in the longitudinal direction and numerical aperture of 2.03, enabling beam focusing and collimation of less than 10 μm between devices with width-scaling ratio of 11. For the fundamental transverse electric field (TE0) mode, the relative transmittance is as high as 96% for forward incidence (from wide to narrow waveguides), whereas the metalens can realize wavefront shaping for backward incidence, which can be used in optical phase arrays. This study provides new ideas for optical interconnect design and wavefront shaping in high-integration PICs. Our design approach has potential applications in directional radiators, LiDAR, on-chip optical information processing, analogue computing, and imaging.

Abstract Campylotropis xinfeniae, a new species from the dry‐hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3‐foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.

Abstract Metasurfaces, 2D arrays of nanostructures, have gained significant attention in recent years due to their ability to manipulate light at the subwavelength scale. Their diverse applications range from advanced optical devices to sensing and imaging technologies. However, the mass production of dielectric metasurfaces with tailored properties for visible light has remained a challenge. Therefore, the demand for efficient and cost‐effective fabrication methods for metasurfaces has driven the continuing development of various techniques. In this research article, a high‐throughput production method is presented for multifunctional dielectric metasurfaces in the visible light range using one‐step high‐index TiO2‐polymer composite (TPC) printing, which is a variant of nanoprinting lithography (NIL) for the direct replication of patterned multifunctional dielectric metasurfaces using a TPC material as the printing ink. The batch fabrication of dielectric metasurfaces is demonstrated with controlled geometry and excellent optical response, enabling high‐performance light‐matter interactions for potential applications of visible meta‐displays.

Background: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular emergency. The incidence of SAH and hazard ratio of death increase with age. Objective: In this study, we aimed to observe the effects and potential mechanisms of olfactory three needle (OTN) on cognitive impairment, neuronal activity, and neural stem cell differentiation in SAH rats. Methods: Sprague-Dawley (SD) rats were randomly divided into five groups: Sham, SAH group, SAH + Nimodipine (NMP) group, and SAH + OTN group. The rats in the SAH + OTN group received the OTN electroacupuncture treatment. For treatment with recombinant DKK1 (a Wnt/β-catenin inhibitor), mice were injected with DKK1. Results: Our results found that OTN improved cognitive impairment and hippocampal neuron damage in SAH rats. Furthermore, OTN promoted the proliferation of neural stem cells in SAH rats. Mechanistically, OTN activated Wnt/β-catenin signaling in SAH rats, as indicated by the increased expression levels of Wnt1, β-Catenin, LMNB1, and p-GSK-3β. DKK1 reversed the improvement effect of OTN on cognitive impairment and neuronal damage in SAH rats. Meanwhile, DKK1 blocked the promoting effect of OTN on the proliferation of NSCs in SAH rats. Conclusions: OTN electroacupuncture may be an effective therapeutic strategy for SAH.

Metalenses have gained significant attention and have been widely utilized in optical systems for focusing and imaging, owing to their lightweight, high-integration, and exceptional-flexibility capabilities. Traditional design methods neglect the coupling effect between adjacent meta-atoms, thus harming the practical performance of meta-devices. The existing physical/data-driven optimization algorithms can solve the above problems, but bring significant time costs or require a large number of data-sets. Here, we propose a physics-data-driven method employing an “intelligent optimizer” that enables us to adaptively modify the sizes of the meta-atom according to the sizes of its surrounding ones. The implementation of such a scheme effectively mitigates the undesired impact of local lattice coupling, and the proposed network model works well on thousands of data-sets with a validation loss of 3×10−3. Based on the “intelligent optimizer”, a 1-cm-diameter metalens is designed within 3 hours, and the experimental results show that the 1-mm-diameter metalens has a relative focusing efficiency of 93.4% (compared to the ideal focusing efficiency) and a Strehl ratio of 0.94. Compared to previous inverse design method, our method significantly boosts designing efficiency with five orders of magnitude reduction in time. More generally, it may set a new paradigm for devising large-aperture meta-devices.

Mazus motuoensis W.B.Ju, Bo Xu bis & X.F.Gao is a newly described species found in Xizang Autonomous Region, China. Morphologically, this species differs from all the other known Mazus species by having erect perennial herb form with a rhizome, presence of multicellular hairs, without basal leaves, opposite arrangement of stem leaves, and corolla lobes with erose-toothed margins. Molecular phylogenetic analysis using nuclear and cpDNA genes suggests that this new species occupies a basal position within Mazus. In conclusion, both morphological evidence and molecular phylogenetic analyses support that this species belongs to Mazus and represents an as-yet-unreported new species with distinct differences from other species within the genus.

Abstract PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265. Phosphorylation is required for the maintenance of UHRF1 protein stability by recruiting a deubiquitinase USP7. Conversely, PLK1 inhibition decreases UHRF1 protein interaction with USP7 and activates the ubiquitin-proteasome pathway, thereby accelerating UHRF1 protein degradation. UHRF1 degradation decreases the recruitment of DNMT1 to chromatin, and decreases the level of genome-wide DNA methylation, thereby elevating the expression of tumor suppressor genes and decreasing cell viability. We here presented the first report on the novel role of PLK1 in DNA methylation maintenance through UHRF1-DNMT1 pathway, and revealed a novel anticancer mechanism of PLK1 inhibitors.

Carrageenans were widely utilized as thickening and gelling agents in the food and cosmetic industries, and their oligosaccharides have been proven to possess enhanced physicochemical and biological properties. In this study, Shewanella sp. LE8 was utilized for the depolymerization of κ-, ι-, and λ-carrageenan under conditions of fermentation. During a 24-h fermentation at 28 °C, the apparent viscosity of κ-, ι-, and λ-carrageenan decreased by 53.12%, 84.10%, and 59.33%, respectively, accompanied by a decrease in storage modulus, and loss modulus. After a 72-h fermentation, the analysis of methylene blue and molecular weight distribution revealed that ι-carrageenan was extensively depolymerized into smaller polysaccharides by Shewanella sp. LE8, while exhibiting partial degradation on κ- and λ-carrageenan. However, the impact of Shewanella sp. LE8 on total sugars was found to be limited; nevertheless, a significant increase in reduced sugar content was observed. The ESIMS analysis results revealed that the purified components obtained through ι-carrageenan fermentation for 72 h were identified as tetrasaccharides, while the two purified components derived from λ-carrageenan fermentation consisted of a hexasaccharide and a tetrasaccharide, respectively. Overall, the present study first reported the depolymerization of ι-and λ-carrageenan by Shewanella and suggested that the Shewanella could be used to depolymerize multiple carrageenans, as well as complex polysaccharides derived from red algae, to further obtain their oligosaccharides.

Weak doping can broaden, shift, and quench plasmon peaks in nanoparticles, but the mechanistic intricacies of the diverse responses to doping remain unclear. In this study, we used the time-dependent density functional theory (TD-DFT) to compute the excitation properties of transition-metal Pd- or Pt-doped gold and silver atomic arrays and investigate the evolution characteristics and response mechanisms of their plasmon peaks. The results demonstrated that the Pd or Pt doping of the off-centered 10 × 2 atomic arrays broadened or shifted the plasmon peaks to varying degrees. In particular, for Pd-doped 10 × 2 Au atomic arrays, the broadened plasmon peak significantly blueshifted, whereas a slight red shift was observed for Pt-doped arrays. For the 10 × 2 Ag atomic arrays, Pd doping caused almost no shift in the plasmon peak, whereas Pt doping caused a substantial red shift in the broadened plasmon peak. The analysis revealed that the diversity in these doping responses was related to the energy positions of the d electrons in the gold and silver atomic clusters and the positions of the doping atomic orbitals in the energy bands. The introduction of doping atoms altered the symmetry and gap size of the occupied and unoccupied orbitals, so multiple modes of single-particle transitions were involved in the excitation. An electron transfer analysis indicated a close correlation between excitation energy and the electron transfer of doping atoms. Finally, the differences in the symmetrically centered 11 × 2 doped atomic array were discussed using electron transfer analysis to validate the reliability of this analytical method. These findings elucidate the microscopic mechanisms of the evolution of plasmon peaks in doped atomic clusters and provide new insights into the rational control and application of plasmons in low-dimensional nanostructures.

In the past, comprehensive information was imperative for image processing, prompting a preference for high-depth cameras. However, in our research, we discovered that the abundance of image details may impede phase retrieval. Consequently, this paper presents an iterative phase retrieval method based on a low bit depth. Through simulations and experiments, this approach has proven effective in evidently enhancing phase retrieval outcomes. Furthermore, the concept of low bit depth holds promise for broader application across diverse domains within the field of image retrieval.

Polysaccharides derived from diverse sources exhibit distinct rheological and gel properties, exerting a profound impact on their applicability in the food industry. In this study, we collected five Gracilaria chouae samples from distinct geographical regions, namely Rizhao (RZ), Lianyungang (LYG), Ningde (ND), Beihai (BH), and a wild source from Beihai (BHW). We conducted analyses on the chemical composition, viscosity, and rheological properties, as well as gel properties, to investigate the influence of chemical composition on variations in gel properties. The results revealed that the total sugar, sulfate content, and monosaccharide composition of G. chouae polysaccharides exhibit similarity; however, their anhydrogalactose content varies within a range of 15.31% to 18.98%. The molecular weight distribution of G. chouae polysaccharides ranged from 1.85 to 2.09 × 103 kDa. The apparent viscosity of the LYG and BHW polysaccharides was relatively high, whereas that of RZ and ND was comparatively low. The gel strength displayed a similar trend. BHW and LYG exhibited solid-like behavior, while ND, RZ, and BH demonstrated liquid-like characteristics at low frequencies. The redundancy analysis (RDA) analysis revealed a positive correlation between the texture profile analysis (TPA) characteristics and anhydrogalactose. The study could provide recommendations for the diverse applications of G. chouae polysaccharides derived from different geographical regions.

Road construction and strip mining in mountainous regions inevitably causes the destruction of vegetation and soil, leading to large ranges of exposed slopes. Although soil spray-sowing has become a promising method to accelerate community assembly in humid regions, the application of microbial fertilizers and shading in slope recovery during soil spray-sowing are rarely reported in dry-hot valleys. This study compared the effectiveness among artificial seeding, arch column + planting bags, and soil spray-sowing by slope restoration trials in the Yuanjiang dry-hot valley, southwest China. Additionally, we explored the effect of slope degrees, shade, and microbial fertilizers on seedling survival and growth after soil spray-sowing. Results indicated that soil spray-sowing displayed better species survival and growth performance than artificial seeding and arch column + planting bags. The richness, density, and height of seedlings dropped dramatically with the increasing of slope degrees after soil spray-sowing, especially when the slope degree was greater than 1. Although shading observably improved the species density, it inhibited the growth of Albizia julibrissin and Crotalaria pallida. Moreover, microbial fertilizers Penicillium chrysogenum and Bacillus aryabhattai markedly enhanced the density and growth of species Azadirachta Indica, Cajanus cajan, Indigofera cassioides, and Sophora xanthanth. Soil spray-sowing, combined with shading and microbial fertilizers, contributes to species survival and growth when the slope degree is less than 1.73 and the soil spray-sowing process coincides with the rainy season, which provides the theoretical basis and technical support for ecological restoration in the dry-hot river valley.

Abstract Dietary methionine interventions are beneficial to apoptosis-inducing chemotherapy and radiotherapy for cancer, while their effects on ferroptosis-targeting therapy and immunotherapy are unknown. Here we show the length of time methionine deprivation affects tumoral ferroptosis differently. Prolonged methionine deprivation prevents glutathione (GSH) depletion from exceeding the death threshold by blocking cation transport regulator homolog 1 (CHAC1) protein synthesis. Whereas, short-term methionine starvation accelerates ferroptosis by stimulating CHAC1 transcription. In vivo, dietary methionine with intermittent but not sustained deprivation augments tumoral ferroptosis. Intermittent methionine deprivation also sensitizes tumor cells against CD8+ T cell-mediated cytotoxicity and synergize checkpoint blockade therapy by CHAC1 upregulation. Clinically, tumor CHAC1 correlates with clinical benefits and improved survival in cancer patients treated with checkpoint blockades. Lastly, the triple combination of methionine intermittent deprivation, system xc - inhibitor and PD-1 blockade shows superior antitumor efficacy. Thus, intermittent methionine deprivation is a promising regimen to target ferroptosis and augment cancer immunotherapy.

Abstract Background Prostate cancer(PCa) is the most commonly occurring male cancer in the USA. Abiraterone or Enzalutamide have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). However, the treatment-emergent neuroendocrine PCa (t-NEPC) may develop, resulting in drug resistance in about 10–17% CRPC patients. The detailed mechanisms remain unclear.. Methods The expression correlation of TOMM20 and AR in PCa was determined by analyzing publicly available datasets, or by IHC staining in tumor specimens. The protein interaction of TOMM20 and AR was validated by co-immunoprecipitation or GST pull-down assay. The impact of TOMM20 depletion on drug sensitivity were elucidated by assays of cell proliferation, invasion, sphere formation, xenograft growth and intravenous metastasis. The intracellular ROS level was measured by flow cytometry, and the NEPC transdifferentiation and characteristics of cancer stem-like cells were validated by RNA-seq, RT-PCR and western blotting. Results The protein level of TOMM20 is positively correlated with AR in PCa cells and specimens. TOMM20 protein physically interacts with AR. AR antagonists induced the protein degradation of TOMM20 through autophagy-lysosomal pathway, thereby elevating the intracellular ROS level and activating PI3K/AKT signaling pathway. When TOMM20 was depleted, PCa cells underwent EMT, acquired the characteristics of cancer stem-like cells, and developed resistance to AR antagonists. The stable depletion of TOMM20 promoted the transdifferentiation of PCa adenocarcinoma into NEPC and metastasis. Conversely, the rescue of TOMM20 re-sensitized the resistant PCa cells to AR antagonists. Conclusions TOMM20 protein degradation induced by AR antagonists promoted the transdifferentiation of PCa to NEPC, thereby revealing a novel molecular mechanism by which AR antagonists develop drug resistance through mitochondrial outer membrane-mediated signaling pathway. These findings suggested that the decreasing or loss of TOMM20 expression in PCa tissues might become a useful predictor of PCa resistance to AR antagonists.

Background: Social isolation can be particularly challenging for individuals with high autistic traits who struggle with social interactions. The COVID-19 pandemic led to increased isolation, exacerbating stress for those who may have difficulty in connecting with others. This study aimed to explore the relationship between autistic traits and stress associated with social isolation. Methods: A sample of 1597 Chinese adults completed measures of autistic traits, the stress of social isolation, psychological inflexibility and core self-evaluation, during an epidemic prevention and control period of COVID-19 in Chongqing, China. Measures included the Autism-Spectrum Quotient, Coronavirus Stress Measure, Acceptance and Action Questionnaire-II, and Core Self-Evaluation Scale. Results: Autistic traits were positively correlated with the stress of social isolation, which was mediated by the chain effect of core self-evaluation and psychological inflexibility. individuals with high autistic traits reported significantly higher stress than individuals with low autistic traits. Limitations: This was a cross-sectional study, which limits causal inference. In addition, data were self-reported, which may cause methodological effects. Finally, this study was conducted during China's quarantine policy and external validation of the findings is required. Conclusions: Autistic traits are positively associated with the stress of social isolation. Autistic traits affected core self-evaluation first, and psychological inflexibility subsequently, leading to the stress of social isolation. individuals with high autistic traits tended to experience higher levels of stress during pandemic quarantines. The findings provide useful evidence for developing interventions and implementing preventive measures to reduce stress in individuals with high autistic traits and autism spectrum disorder.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Our main objective was to examine the curative effect of all inside technique and traditional technique in anterior cruciate ligament (ACL) reconstruction. In our retrospective study at the First People's Hospital of Jiashan County, we analyzed 88 participants with ACL injuries (50 males, 38 females, average age 27 years). They were randomly divided into two groups: traditional ACL reconstruction (42 participants) and all inside ACL reconstruction (46 participants). We measured and recorded the Visual Analog Scores (VAS), International Knee Documentation Committee (IKDC), Lysholm scores, operation time, graft diameter and length between the traditional technique group and all inside technique group. There were statistically significant differences in the Lysholm scores and IKDC scores between traditional and all inside technique groups. The all inside technique showed a higher efficacy and effective post-operative recovery with minimal pain and recurrent injuries. Our findings showed that the differences in gender, age, side of injury and operation time were not significant (p> 0.05). Follow-up was conducted at 6 months and 12 months post operations (mean, 7.5 ± 1.1 months). All inside technique minimizing tissue disruption, optimizing graft placement and facilitating early recovery have a significant impact on patient outcomes.

Introduction: The excretion and absorption of uric acid (UA) by the kidneys helps regulate serum UA levels. GLUT9, encoded by SLC2A9, is mainly expressed in the renal tubules responsible for UA absorption. SLC2A9 polymorphisms are associated with different serum UA levels. However, the lack of proper in vitro models has stalled research on the mechanisms of single nucleotide polymorphisms (SNPs) that affect UA metabolism in human urate transporters.Methods: In this study, we constructed a gene-edited human embryonic stem cells-9 (ESC-H9) derived kidney organoid bearing rs16890979, an SLC2A9 missense mutation with undetermined associations with hyperuricemia or hypouricemia. Kidney organoids derived from ESC-H9 with genetical overexpression (OE) and low expression (shRNA) of SLC2A9 to serve as controls to study the function of SLC2A9. The function of rs16890979 on UA metabolism was evaluated after placing the organoids to urate-containing medium and following histopathological analysis.Results: The kidney organoids with heterozygous or homozygous rs16890979 mutations showed normal SLC2A9 expression levels and histological distribution, phenotypically similar to the wild-type controls. However, reduced absorption of UA by the kidney organoids with rs16890979 mutants was observed. This finding together with the observation that UA absorption is increased in organoids with SLC2A9 overexpression and decreased in those with SLC2A9 knockdown, suggest that GLUT9 is responsible for UA absorption, and the rs16890979 SNP may compromise this functionality. Moreover, epithelial-mesenchymal transition (EMT) was detected in organoids after UA treatment, especially in the kidney organoid carrying GLUT9OE, suggesting the cytobiological mechanism explaining the pathological features in hyperuricosuria-related renal injury.Discussion: This study showing the transitional value of kidney organoid modeling the function of SNPs on UA metabolism. With a defined genetic background and a confirmed UA absorption function should be useful for studies on renal histological, cellular, and molecular mechanisms with this organoid model.

In the era of big data, competent medical care has entered people’s lives. However, the existing intelligent diagnosis models have low accuracy and poor universality. At the same time, there is a risk of privacy leakage in the process of health monitoring and auxiliary diagnosis. This paper combines edge computing and federated learning ensure model accuracy and protect patient privacy by proposing an Edge intelligent collaborative privacy protection solution for smart medical (EICPP). First, we offer a lightweight edge intellectual collaborative federated learning framework named KubeFL to support health monitoring and auxiliary diagnosis; secondly, we design a federated learning training model based on device-edge-cloud layering, with complete accuracy of up to 95.8%; Finally, a differential privacy algorithm for edge-cloud model transmission is proposed, which can exchange a lower accuracy loss for solid privacy protection.

AbstractObjectives Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation (TLPMA) is a minimally invasive alternative technique with low risk, fast recovery and few side effects. We aimed to evaluate the safety and long-term efficacy of TLPMA for treating adenomyosis.Methods We included 79 patients with symptomatic adenomyosis who underwent TLPMA and 44 patients with adenomyosis who received the levonorgestrel-releasing intrauterine system (LNG-IUS). We evaluated the role of laparoscopy in TLPMA as well as the short- and long-term effects of TLPMA.Results The mean age of the 79 patients who underwent TLPMA was 41.8 years. There was no difference in the mean age between the TLPMA and LNG-IUS groups. Laparoscopy could help to separate pelvic adhesions, provide a wide antenna path, and observe the uterine surface and bowel movement. No major complications were found in patients who underwent TLPMA. There was a significant post-treatment reduction in both the uterine and lesion volumes (p

Objective To determine the effect of carnitine palmitoyl-transferase 1A (CPT1A) on renal interstitial fibrosis in diabetic kidney disease (DKD). Methods A total of 16 4-week-old male C57BL/6 mice were randomly divided into Control (Ctrl) group (n=8) and DKD group (n=8). The mice of Ctrl group were fed with normal diet, and those from the DKD group were inflicted with intraperitoneal streptozotocin injection plus high fat diet (STZ/HFD) to induce DKD model. Their 24-hour urine were collected, and fasting blood glucose level and body weight were measured every 4 weeks. After 16 weeks of modeling, the mice (aged 20 weeks) were sacrificed, and the levels of serum creatinine, urine creatinine and urine albumin were measured. PAS and Masson stainings were used to analyze the renal glomerulus morphology and interstitial fibrosis. Immunohistochemical assay and Western blotting were performed to detect the expression of CPT1A and fibrosis markers. In in vitro study, human proximal tubular epithelial HK-2 cells were divided into Ctrl group, HG group (30 mmol/L glucose treatment), and M group (30 mmol/L mannitol treatment). After treatment for 48 h, the protein levels of CPT1A and fibrosis markers were detected with Western blotting. After HK-2 cells were transfected with CPT1A overexpression plasmid and then treated with 30 mmol/L glucose, cell morphological changes and the expression of CPT1A and fibrosis markers were observed. Results The mice of the DKD group had obvious glomerulus hypertrophy, mesangial expansion and renal interstitial fibrosis, increased levels of serum creatinine and urine albumin/creatinine ratio (P < 0.05), decreased CPT1A expression, and elevated protein levels of fibrosis markers when compared with the mice of the Ctrl group. In in vitro experiment, HG treatment induced the morphological changes of HK-2 cells into long spindle-shape, decreased level of CPT1A, and increased levels of fibrosis markers, which were not affected by alterations of osmotic pressure. However, CPT1A overexpression significantly reversed these HG-induced morphological changes and high expression of fibrosis markers. Conclusion Overexpression of CPT1A may show potential inhibitory effect on renal interstitial fibrosis in DKD mice.

Usual methods for optical encryption suffer from a tradeoff between the level of security and the complexity of operation given by multiple optical measurements or digital postprocessing. Here, the authors show a multi-d.o.f. metasurface-based vector optical manipulation protocol enabling secure decryption in real time.

Background: Presenilin enhancer-2 (PSENEN, PEN-2), one of the four components of the γ-secretase complex, has been increasingly revealed to be significant in cancer types such as pancreatic cancer, gastric cancer, and breast cancer. However, the pan-cancer clinical relevance of PSENEN remains unclear. Methods: Raw data on PSENEN expression in normal and cancer tissues were obtained from The Cancer Genome Atlas (TGCA) database and Genotype-Tissue Expression Project (GTEx). The difference of PSENEN expression was analyzed using data from the TCGA repository and TIMER2 database. Meanwhile, Cox regression analysis and KM plotter were used to analyze the pan-cancer prognostic significance of PSENEN. We also analyzed the correlation between PSENEN expression and tumor immune infiltration using the TIMER and XCELL algorithms. Moreover, we used the TISIDB database to determine PSENEN expression in different immune and molecular subtypes of human cancers. Pan-cancer analysis of genetic alteration of PSENEN was performed using online tools such as cBioPortal and UALCAN. Finally, six Gene Expression Omnibus datasets from the Gene Expression Profiling Interactive Analysis database were used to validate the expression level of PSENEN in lung adenocarcinoma (LUAD). Results: Contrary to nonmalignant tissues, the expression level of PSENEN was significantly upregulated in the cancerous tissues in 22 cancer types. Elevated PSENEN expression was correlated with worse overall survival in 7 cancer types and with worse disease-specific survival in 8 of them. By using xCell algorithm, TIMER algorithm, and Spearman's correlation analysis, we found that PSENEN expression was closely correlated with the infiltration of immune cells across all cancer types. Moreover, aberrant PSENEN expression was associated with 60 immune checkpoint pathway-related genes, microsatellite instability, and tumor mutation burden in various cancer types. Besides, PSENEN expression was significantly associated with different immune subtypes and molecular subtypes of various human cancers. Notably, ovarian epithelial tumor samples demonstrated the highest frequency of PSENEN mutation among all cancer types. Conclusions: Our pan-cancer analysis demonstrated that PSENEN might serve as a prognostic biomarker and revealed the importance of an in-depth understanding of the oncogenic role of PSENEN in various malignancies.

The limestone region in Southwest Guangxi is defined as a priority area for biodiversity conservation and research not only at provincial but also at national level. Through in-depth investigation in the two nature reserves of this region, 20 angiosperm species from 20 genera and 17 families were found as new records for the flora of Guangxi, including Wuodendron praecox (Hook. f. & Thomson) B. Xue, Y. H. Tan & X. L. Hou, Phoebe macrocarpa C. Y. Wu, Clematis fengii W. T. Wang, Trichosanthes tetragonosperma C. Y. Cheng & Yueh, Sorbus yunnanensis L. T. Lu, Elatostema longibracteatum W. T. Wang, Acer paihengii Fang, Cornus eydeana Q. Y. Xiang & Y. M. Shui, Rhododendron longipedicellatum Lei Cai & Y. P. Ma, Styrax roseus Dunn, Symplocos hookeri C. B. Clarke, Dicercoclados triplinervis C. Jeffrey & Y. L. Chen, Lysimachia pittosporoides C. Y. Wu, Lycianthes marlipoensis C. Y. Wu & S. C. Huang, Justicia multinodis Benoist, Scutellaria sichourensis C. Y. Wu & H. W. Li, Liparis bistriata C. S. P. Parish & Rchb. f., Peristylus tenuicallus Ormerod, Pinalia yunnanensis (S. C. Chen & Z. H. Tsi) S. C. Chen & J. J. Wood and Zeuxine integrilabella C. S. Leou. Among them, Wuodendron B. Xue, Y. H. Tan & Chaowasku and Dicercoclados C. Jeffrey & Y. L. Chen were new recorded genera of Guangxi. All species were annotated by morphological and distribution description, voucher specimens and pictures. In addition, based on collected materials, several key taxonomic characteristics of Trichosanthes tetragonosperma C. Y. Cheng & Yueh and Dicercoclados triplinervis C. Jeffrey & Y. L. Chen were supplemented and revised respectively. Lastly, the biogeographic significance of these newly records as well as protection effectiveness of the reserves in limestone region of southwestern Guangxi were discussed.

Abstract Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer‐specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti‐tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen‐based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen‐based therapy holds great promise as an effective treatment approach for patients with CRC.

Background: Gu-ben-hua-shi (AESS) formula is a clinical experienced prescription from Guangdong Hospital of Traditional Chinese Medicine (TCM), which is used to treat atopic dermatitis (AD). Our previous work has shown that AESS has therapeutic effect on AD by regulating yes-associated protein (YAP). AESS formula has multi-component and multi-target characteristic, and need to be analyzed by systematic chemical profiling and network pharmacology technology, as well as verification of key signaling pathways. Therefore, this study aimed at investigating the efficacy and effect of AESS formula in the treatment of AD and its effect on NLRP3 signaling pathway. Methods: The components of AESS formula were analyzed and identified by ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC- MS/MS), and the potential mechanism of AESS formula in the treatment of AD was predicted by network pharmacology approach, with detected main components, and the potential components targeted NOD-like receptor thermal protein domain associated protein (NLRP3) signaling pathway [Direct binding with NLRP3, apoptosis-associated speck-like protein (ASC) and Caspase-1] were assessed using molecular docking. AD-like symptoms were constructed by DNCB induced BALB/c mice. The effect of AESS formula on dorsal skin structure in AD-like mice was observed using H&E staining. Furthermore, the western blotting experiment explored the expression of the NLRP3 pathway protein. Results: By UHPLC-MS/MS analysis, 91 compounds were detected in AESS formula, and 76 of them were identified, while by network pharmacological analysis, 1500 component targets were obtained, and 257 of them were obtained by intersection with eczema targets. Then one of the key pathways, nucleotide-binding oligomerization domain (NOD)-like signaling pathway was obtained by KEGG enrichment analysis. Molecular docking results showed 24 main components could effectively combine with ASC and Caspase-1 (≤−7 kcal/mol). The animal experiment results further showed that AESS formula alleviates symptoms in AD-like mice. ELISA kit results showed that the expression of IL-1β and IL-18 in serum was inhibited after AESS treatment. Additionally, western blotting analysis showed that the expressions of ASC, Caspase-1 and NLRP3 protein expression in the skin tissue of mice were down-regulated after AESS treatment. The experimental results show that AESS formula inhibited the expression of NLRP3 signaling pathway for the treatment of AD. Conclusions: AESS formula can improve AD symptoms in mice by inhibiting the activation of NLRP3 inflammasome and the expression of the related downstream inflammatory cytokines.

Abstract A deep understanding of the complex interaction mechanism between the various cellular components in tumor microenvironment (TME) of lung adenocarcinoma (LUAD) is a prerequisite for understanding its drug resistance, recurrence, and metastasis. In this study, we proposed two complementary computational frameworks for integrating multi-source and multi-omics data, namely ImmuCycReg framework (single sample level) and L0Reg framework (population or subtype level), to carry out difference analysis between the normal population and different LUAD subtypes. Then, we aimed to identify the possible immune escape pathways adopted by patients with different LUAD subtypes, resulting in immune deficiency which may occur at different stages of the immune cycle. More importantly, combining the research results of the single sample level and population level can improve the credibility of the regulatory network analysis results. In addition, we also established a prognostic scoring model based on the risk factors identified by Lasso-Cox method to predict survival of LUAD patients. The experimental results showed that our frameworks could reliably identify transcription factor (TF) regulating immune-related genes and could analyze the dominant immune escape pathways adopted by each LUAD subtype or even a single sample. Note that the proposed computational framework may be also applicable to the immune escape mechanism analysis of pan-cancer.

The shale oil exploration, in the Middle Jurassic Lianggaoshan Formation in the Fuxing area of Sichuan Basin, is in preliminary stage, requiring further in-depth study on shale oil and gas enrichment conditions. The lithological, organic geochemical, and reservoir characteristics of the Lianggaoshan Formation shale were analyzed using a suite of tests, including common thin section observation, organic carbon determination, pyrolysis experiment, combined N2-high pressure mercury test and argon ion polishing-scanning electron microscope, to elucidate source rock and reservoir qualities and their variation in vertical. Results suggest that the medium-carbon argillaceous shale, medium-carbon shell calcareous-argillaceous shale, and low-carbon argillaceous shale facies were mainly developed in Member 1 and Member 2 of the Lianggaoshan Formation. The medium-carbon argillaceous shale facies in the sub-layer ④ was rich in organic matter, with abundant sapropel, chitinous and secondary organic components, which were considered as a set of medium-quality source rocks. The medium-carbon shell calcareous-argillaceous shale and low-carbon argillaceous shale in the sub-layers ② and ③ have relatively low organic matter abundance, with vitrinite and inertinite as major organic microscopic components, revealing poor hydrocarbon generation potential. The porosity of shale reservoirs in sub-layers ②‒④ was higher than 3.0%, with predominant mesopores, followed by macropores, consisting of mainly clay mineral pores, organic pores, and microfractures related to organic matter. The medium-carbon argillaceous shale facies at the Lianggaoshan Formation is high-quality source rocks and reservoirs and is thus a potential target for lacustrine shale oil exploration in the Fuxing area of the Sichuan Basin.

The imbalanced data makes the machine learning model seriously biased, which leads to false positive in screening of therapeutic drugs for breast cancer. In order to deal with this problem, a multi-model ensemble framework based on tree-model, linear model and deep-learning model is proposed. Based on the methodology constructed in this study, we screened the 20 most critical molecular descriptors from 729 molecular descriptors of 1974 anti-breast cancer drug candidates and, in order to measure the pharmacokinetic properties and safety of the drug candidates, the screened molecular descriptors were used in this study for subsequent bioactivity, absorption, distribution metabolism, excretion, toxicity, and other prediction tasks. The results show that the method constructed in this study is superior and more stable than the individual models used in the ensemble approach.

This paper describes and illustrates a new species of Primulaceae, Primula wolongensis sp. nov. from Wolong National Nature Reserve in Sichuan Province, China. It is very rare and currently only known from its type locality. The new species belongs to subsection Chartacea of the section Petiolares on account of lacking bud scales at flowering, being efarinose and having distinct petiolate leaves with more or less rounded lamina. The new species can be differentiated from other members of the subsection by leaf blade margin dentate, and leaf veins which are not raised, scape shorter than or equal to pedicels, yellow flowers and location of stamens of the corolla tube at thrum flower. Molecular phylogenetic analysis based on nuclear ribosome internal transcribed spacer (nrITS) demonstrated that P. wolongensis was sister to subgen. Auriculastrum. Primula wolongensis is currently known from a single location in Wolong Town, and its conservation status is assessed as Data Deficient (DD).

Abstract Oncogenic activation of PI3K/AKT signaling pathway, together with epigenetic aberrations are the characters of castration-resistant prostate cancer (CRPC). UHRF1 as a key epigenetic regulator, plays a critical role in prostate cancer (PCa) development, and its expression is positively correlated with the degree of malignancy. In this present study we investigated the potential regulatory mechanism of AKT1 on UHRF1, and further validated the in vitro and in vivo anticancer efficacy of AKT phosphorylation inhibitor MK2206 in combination with abiraterone. Both UHRF1 and p-AKT aberrantly overexpressed in the abiraterone-resistant PCa cells. Further studies revealed that AKT1 protein interacts with UHRF1, and AKT1 directly phosphorylates UHRF1 via the site Thr-210. MK2206 induced UHRF1 protein degradation by inhibiting AKT1-induced UHRF1 phosphorylation, and then reduced the interaction between UHRF1 and deubiquitinase USP7, while promoted the interaction between UHRF1 and E3 ubiquitin protein ligase BTRC. MK2206 significantly promoted the sensitivity of abiraterone-refractory PCa cells and xenografts to abiraterone by decreasing UHRF1 protein level, and reversed the phenotype of NEPC, evently induced cellular senescence and cell apoptosis. Altogether, our present study for the first time revealed a novel molecular mechanism of abiraterone resistance through PI3K/AKT-UHRF1 pathway, and provided a novel therapeutic modality by targeting PI3K/AKT1 to promote the drug sensitivity of abiraterone in PCa patients.

Abstract The aim of this study is to find those N7-methylguanosine (m7G) methylation-related regulator genes (m7GMRRGs) which were associated with melanoma prognosis and use them to develop a prognostic prediction model. Clinical information was retrieved online from The Cancer Gene Atlas (TCGA) and the Gene Expression Omnibus (GEO). R software was used to extract m7GMRRGs by differential expression analysis. To create a prognostic risk model, univariate and multivariate Cox regression analyses were employed for the evaluation of the prognostic significance of m7G methylation modifiers. Internal validation using cohort from TCGA (training set) and external validation using cohort from GEO (validation set) of the model were carried out. The model’s predictive performance was confirmed by using the Kaplan–Meier, univariate, and multivariate Cox regression, and receiver operating characteristic curve (ROC) by constructing column line plots incorporating clinical factor characteristics. Immune infiltration analyses were performed to assess the immune function of m7GMRRGs. Drug sensitivity analysis was conducted to study chemotherapeutic drug treatment cues. Prognostic models using four m7GMRRGs (EIF4E3, LARP1, NCBP3, and IFIT5) showed good prognostic power in training and validation sets. The area under the curve (AUC) at 1, 3, and 5 years for GEO-melanoma were 0.689, 0.704, and 0.726, respectively. The prediction model could distinctly classify patients with melanoma into different risk subgroups (P

The GGGGCC (G4C2) hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia. Recent studies have shown that G4C2 hexanucleotide repeat-containing RNA transcripts ((G4C2)n RNA) could go through liquid-liquid phase separation to form RNA foci, which may elicit neurodegeneration. However, the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated. Here we introduce an optogenetic control system that can induce the assembly and phase separation of (G4C2)n RNA foci with blue light illumination in human cells, by fusing a specific (G4C2)n RNA binding protein as the linker domain to Cry2, a protein that oligomerizes in response to blue light. Our results demonstrate that a higher number of G4C2 repeats have the potential to be induced into more RNA foci in the cells. Both spontaneous and induced RNA foci display liquid-like properties according to FRAP measurements. Computational simulation shows strong consistency with the experimental results and supports the effect of our system to promote the propensity of (G4C2)n RNA towards phase separation. This system can thus be used to investigate whether (G4C2)n RNA foci would disrupt normal cellular processes and lead to pathological phenotypes relevant to repeat expansion disorders.