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Abstract Background Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. Methods Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT–PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl–biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. Results We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. Conclusions Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC. Graphical Abstract

Poisson's ratio in auxetic materials shifts from typically positive to negative, causing lateral expansion during axial tension. This scale‐independent characteristic, originating from tailored architectures, exhibits specific physical properties, including energy adsorption, shear resistance, and fracture resistance. These metamaterials demonstrate exotic mechanical properties with potential applications in several engineering fields, but biomedical applications seem to be one of the most relevant, with an increasing number of articles published in recent years, which present opportunities ranging from cellular repair to organ reconstruction with outstanding mechanical performance, mechanical conduction, and biological activity compared with traditional biomedical metamaterials. Therefore, focusing on understanding the potential of these structures and promoting theoretical and experimental investigations into the benefits of their unique mechanical properties is necessary for achieving high‐performance biomedical applications. Considering the demand for advanced biomaterial implants in surgical technology and the profound advancement of additive manufacturing technology that are particularly relevant to fabricating complex and customizable auxetic mechanical metamaterials, this review focuses on the fundamental geometric configuration and unique physical properties of negative Poisson's ratio materials, then categorizes and summarizes auxetic material applications across some surgical departments, revealing efficacy in joint surgery, spinal surgery, trauma surgery, and sports medicine contexts. Additionally, it emphasizes the substantial potential of auxetic materials as innovative biomedical solutions in orthopedics and demonstrates the significant potential for comprehensive surgical application in the future.

The transmission and prevalence of Hand, Foot and Mouth Disease (HFMD) are affected by a variety of natural and socio-economic environmental factors. This study aims to quantitatively investigate the non-stationary and spatially varying associations between various environmental factors and HFMD risk. We collected HFMD surveillance cases and a series of relevant environmental data from 2013 to 2021 in Xi'an, Northwest China. By controlling the spatial and temporal mixture effects of HFMD, we constructed a Bayesian spatiotemporal mapping model and characterized the impacts of different driving factors into global linear, non-stationary and spatially varying effects. The results showed that the impact of meteorological conditions on HFMD risk varies in both type and magnitude above certain thresholds (temperature: 30 °C, precipitation: 70 mm, solar radiation: 13000 kJ/m2, pressure: 945 hPa, humidity: 69%). Air pollutants (PM2.5, PM10, NO2) showed an inverted U-shaped relationship with the risk of HFMD, while other air pollutants (O3, SO2) showed nonlinear fluctuations. Moreover, the driving effect of increasing temperature on HFMD was significant in the 3-year period, while the inhibitory effect of increasing precipitation appeared evident in the 5-year period. In addition, the proportion of urban/suburban/rural area had a strong influence on HFMD, indicating that the incidence of HFMD firstly increased and then decreased during the rapid urbanization process. The influence of population density on HFMD was not only limited by spatial location, but also varied between high and low intervals. Higher road density inhibited the risk of HFMD, but higher night light index promoted the occurrence of HFMD. Our findings further demonstrated that both ecological and socioeconomic environmental factors can pose multiple driving effects on increasing the spatiotemporal risk of HFMD, which is of great significance for effectively responding to the changes in HFMD epidemic outbreaks.

Eucommia ulmoides (EU) is a precious tree species native to China originating during the ice age. This species has important economic value and comprehensive development potential, particularly in medicinal applications. The medicinal parts of EU are its bark (Eucommiae cortex) and leaves (Eucommiae folium) which have been successively used as a traditional Chinese medicine to treat diseases since the first century BC. During the last 2 decades, as natural polysaccharides have become of increasing interest in pharmacology, biomedicine, cosmetic and food applications, more and more scholars have begun to study polysaccharides derived from EU as well. EU polysaccharides have been found to have a variety of biological functions both in vivo and in vitro, including immunomodulatory, antioxidant, anti-inflammatory, anticomplementary, antifatigue, and hepatoprotective activities. This review aims to summarize these recent advances in extraction, purification, structural characteristics, pharmacological activities and applications in different fields of EU bark and leaf polysaccharides. It was found that both Eucommiae folium polysaccharides and Eucommiae cortex polysaccharides were suitable for medicinal use. Eucommiae folium may potentially be used to substitute for Eucommiae cortex in terms of immunomodulation and antioxidant activities. This study serves as a valuable reference for improving the comprehensive utilization of EU polysaccharides and further promoting the application of EU polysaccharides.

BackgroundHemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory.MethodsWe analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence.ResultsA total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months.ConclusionsOur discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.

Prime Power RSA is a variant of the RSA scheme due to Takagi with modulus N=prq for r⩾2, where p,q are of the same bit-size. In this paper, we concentrate on one type of Prime Power RSA which assumes e·d≡1modpr−1(p−1)(q−1). Two new attacks on this type of Prime Power RSA are presented when given two pairs of public and private exponents, namely, (e1,d1) and (e2,d2) with the same modulus N. Suppose that d1

Summary: M2 macrophages are associated with the prognosis of bladder cancer. CLDN6 has been linked to immune infiltration and is crucial for predicting the prognosis in multi-tumor. The effect of CLDN6 on M2 macrophages in bladder cancer remains elusive. Here, we compared a total of 40 machine learning algorithms, then selected optimal algorithm to develop M2 macrophages-related signature (MMRS) based on the identified M2 macrophages related module. MMRS predicted the prognosis better than other models and associated to immunotherapy response. CLDN6, as an important variable in MMRS, was an independent factor for poor prognosis. We found that CLDN6 was highly expressed and affected immune infiltration, immunotherapy response, and M2 macrophages polarization. Meanwhile, CLDN6 promoted the growth of bladder cancer and enhanced the carcinogenic effect by inducing polarization of M2 macrophages. In total, CLDN6 is an independent risk factor in MMRS to predict the prognosis of bladder cancer.

Porphyra haitanensis (P. haitanensis), an important food source for coastal residents in China, has a long history of medicinal and edible value. P. haitanensis polysaccharides are some of the main active ingredients in P. haitanensis. It is worth noting that P. haitanensis polysaccharides have a surprising and satisfactory biological activity, which explains the various benefits of P. haitanensis to human health, such as anti-oxidation, immune regulation, anti-allergy, and anticancer properties. Hence, a systematic review aimed at comprehensively summarizing the recent research advances in P. haitanensis polysaccharides is necessary for promoting their better understanding. In this review, we systematically and comprehensively summarize the research progress on the extraction, purification, structural characterization, modification, and biological activity of P. haitanensis polysaccharides and address the shortcomings of the published research and suggest area of focus for future research, providing a new reference for the exploitation of polysaccharides from P. haitanensis in the fields of medicine and functional foods.

Digital sequence information on genetic resources (hereinafter called DSI) refers to data generated through sequencing technologies. It consists of a broad range of genetic sequence data, which includes the digitalized details of an organism’s DNA and RNA, and chemical structure information of natural products. Considering its significance, DSI has become a hot-button issue of discussions around international treaties such as the Convention on Biological Diversity, the International Treaty on Plant Genetic Resources for Food and Agriculture, and the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits, with particular focus on its access, use, and benefit-sharing process. Since 2016, fruitful discussions have been made among stakeholders about DSI’s access and use, albeit disagreements remain in some areas, examples of which are the connotation and denotation of the placeholder term, DSI’s relevance to genetic resources, the definition of open access, the monitoring of DSI use. Through analytical research of DSI itself and controversies arising from it, we come to the following observations: Science advice alone is not enough to mitigate the differences originating from the conflict of interests between stakeholders; DSI’s placeholder status has made the fulfillment of the benefit-sharing obligation to it more complex; The large variety of domestic regulations around DSI that exist in parties implies that the setup of a feasible, multilateral international system is no easy task; An approach that coordinates different framework conventions is urgently needed to tackle the ongoing challenges facing DSI. To effectively cope with the challenges and opportunities brought by DSI’s access and use, China, as a major provider and user of DSI in the world, should intensify efforts made in the following four areas: (1) Fundamental researches on DSI; to this end, we should encourage the adoption of interdisciplinary approaches in DSI research and introduce pilot demonstration projects on access to and benefit-sharing of DSI; (2) The timely establishment of biological data administration system; we should construct a comprehensive system of biological resource data made up of crucial components including classification, convergence, sharing, research, utilization, cross-border transmission, and benefit-sharing; (3) Infrastructure development that increase the openness, safety, sharing, and reciprocity of the production and storage of global biological resource data; we should strengthen international cooperation in this regard; (4) Better use of the cross-departmental coordination mechanism that involves organizations represented by the China National Committee for Biodiversity Conservation (CNCBC), we should continue to increase the synergy effects originated from China’s greater participation in international fora on DSI.

Eurya rubiginosa var. attenuata is a valuable multiuse tree with a long history of use in China. It has great economic and ecological importance and is used for landscape and urban planting, soil improvement, and raw materials for food production. However, genomic studies of E. rubiginosa var. attenuata are limited. Meanwhile, the classification of this taxon is controversial. In this study, the complete plastome of E. rubiginosa var. attenuata was successfully sequenced and assembled. The chloroplast genome is 157,215 bp in length with a 37.3% GC content. The chloroplast genome structure includes a quadripartite structure comprising a pair of inverted repeat (IR) sequences of 25,872 bp, a small single-copy (SSC) region of 18,216 bp, and a large single-copy (LSC) region of 87,255 bp. The genome contains 128 genes, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic inference based on complete plastome analysis showed that E. rubiginosa var. attenuata is closely related to E. alata and belongs to the family Pentaphylacaceae, which differs from the results of the traditional Engler system. The chloroplast genome sequence assembly and phylogenetic analysis enrich the genetic resources of Pentaphylacaceae and provide a molecular basis for further studies on the phylogeny of the family.

Abstract Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient‐derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d‐bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient‐derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient‐derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

Abstract Background As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis. Methods Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry. Results We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients. Conclusions The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.

ABSTRACT Currently approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultralow-temperature storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed, which offer broader immunity but require significant time for development and the use of an adjuvant to boost the immune response. Here, exosomes were used to deliver a bivalent protein-based vaccine in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 delta spike (Stealth X-Spike [STX-S]) or the more conserved nucleocapsid (Stealth X-Nucleocapsid [STX-N]) protein on the surface. When administered as a single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced strong immunization with the production of potent humoral and cellular immune responses. Interestingly, these results were obtained with the administration of only nanograms of protein and without an adjuvant. In two independent animal models (mouse and rabbit), the administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike, and strong T-cell responses. Importantly, no competition of immune responses was observed, allowing the delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthX exosome platform has the enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low-dose vaccine resulting in potent, broader immunity. IMPORTANCE The pandemic emergency has brought to light the need for a new generation of rapidly developed vaccines that induce longer-lasting, potent, and broader immune responses. While the mRNA vaccines played a critical role during the emergency in reducing SARS-CoV-2 hospitalization rates and deaths, more efficient approaches are needed. A multivalent, protein-based vaccine delivered by exosomes could meet this urgent need due to the high speed of development, manufacturability, and the ability to produce a strong antibody response, with neutralizing antibodies and a strong T-cell response able to broadly combat viral infection with a minimum number of injections.

In this study, we obtained the intensity and orbital angular momentum (OAM) spectral distribution of the scattering fields of vortex electromagnetic beams illuminating electrically large targets composed of different materials. We used the angular spectral decomposition method to decompose a vortex beam into plane waves in the spectral domain at different elevations and azimuths. We combined this method with the physical optics algorithm to calculate the scattering field distribution. The OAM spectra of the scattering field along different observation radii were analyzed using the spiral spectrum expansion method. The numerical results indicate that for beams with different parameters (such as polarization, topological charge, half-cone angle, and frequency) and targets with different characteristics (such as composition), the scattering field intensity distribution and OAM spectral characteristics varied considerably. When the beam parameters change, the results of scattering from different materials show similar changing trends. Compared with beams scattered by uncoated metal and dielectric targets, the scattering field of the coating target can better maintain the shape and OAM mode of beams from the incident field. The scattering characteristics of metal targets were the most sensitive to beam-parameter changes. The relationship between the beam parameters, target parameters, the scattering field intensity, and the OAM spectra of the scattering field was constructed, confirming that the spiral spectrum of the scattering field carries the target information. These findings can be used in remote sensing engineering to supplement existing radar imaging, laying the foundation for further identification of beam or target parameters.

The integration of a renewable energy and hybrid energy storage system (HESS) into electrified railways to build an electric railway smart microgrid system (ERSMS) is beneficial for reducing fossil fuel consumption and minimizing energy waste. However, the fluctuations of renewable energy generation and traction load challenge the effectiveness of the energy management for such a complex system. In this work, an energy management strategy is proposed which firstly decomposes the renewable energy into low-frequency and high-frequency components by an integrated empirical mode decomposition (IEMD). Then, a two-stage energy distribution approach is utilized to appropriately distribute the energy flow in the ERSMS. Finally, the feasibility and effectiveness of the proposed solution are validated through case study.

Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

Abstract This paper proposes modelling on the transmission torque of an eddy‐current axial magnetic coupling (EAMC) considering the thermal effect. A new and simple equivalent reluctance network is established to obtain the magnetic flux density based on the two‐dimensional (2D) finite‐element analysis. Furthermore, the expressions of the transmission torque and the thermal loss are derived by establishing the computational coordinate system for the conductor sheet (CS) eddy current. Then, a simple and effective thermal network considering different convective heat transfer modes is presented to obtain the temperature rise, and the influence of temperature on some key parameters is given to correct the transmission torque. Furthermore, the proposed modelling is in good agreement with the three‐dimensional (3D) finite‐element method (FEM) and experiments under normal working conditions. Moreover, some suggestions for the design and optimization of EAMCs are provided.

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor's StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthXTM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements necessary for mRNA vaccines. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

With the booming of worldwide agriculture intensification, brucellosis, one of the most neglected zoonotic diseases, has become an increasing challenge for global public health. Although the transmission patterns of human brucellosis (HB) have been studied in many regions, the dynamic transfer processes of risk and its driving factors remain poorly understood, especially in the context of agricultural intensification. This study attempted to explore the risk transfer of HB between the exact epidemic areas and the neighboring or distant low-risk areas to explain the impact of livestock agriculture intensification and foodborne infections on the transmission of HB in Shaanxi Province as a case study. We adopted multiple approaches, including test-based methods, model-based methods, and a geographical detector to detect the spatial-temporal dynamic changes of high-risk epidemic areas of HB at the county scale. We also quantitatively estimated how the related factors drove the risk transfer of the disease. Results confirmed the risk transfer pattern of HB with an expansion from north to south in Shaanxi Province and identified two primary transfer routes. In particular, in the traditional epidemic areas of the Shaanbei plateau, the farm agglomeration effect can significantly increase the risk of HB. Meanwhile, retail outlets for milk and dairy products were partially responsible for the foodborne infections of HB in the emerging epidemic areas of Xi'an. This study not only contributed helpful insights to support HB control and prevention in the rapid transition of livestock agriculture but also provided possible directions for further research on foodborne HB infections in urbanized areas.

BackgroundNon-pharmaceutical interventions (NPIs) against COVID-19 may prevent the spread of other infectious diseases. Our purpose was to assess the effects of NPIs against COVID-19 on infectious diarrhea in Xi'an, China.MethodsBased on the surveillance data of infectious diarrhea, and the different periods of emergence responses for COVID-19 in Xi'an from 2011 to 2021, we applied Bayesian structural time series model and interrupted time series model to evaluate the effects of NPIs against COVID-19 on the epidemiological characteristics and the causative pathogens of infectious diarrhea.FindingsA total of 102,051 cases of infectious diarrhea were reported in Xi'an from 2011 to 2021. The Bayesian structural time series model results demonstrated that the cases of infectious diarrhea during the emergency response period was 40.38% lower than predicted, corresponding to 3,211 fewer cases, during the COVID-19 epidemic period of 2020–2021. The reduction exhibited significant variations in the demography, temporal and geographical distribution. The decline in incidence was especially evident in children under 5-years-old, with decreases of 34.09% in 2020 and 33.99% in 2021, relative to the 2017–2019 average. Meanwhile, the incidence decreased more significantly in industrial areas.InterpretationNPIs against COVID-19 were associated with short- and long-term reductions in the incidence of infectious diarrhea, and this effect exhibited significant variations in epidemiological characteristics.

Neovascularization is one of the many manifestations of ocular diseases, including corneal injury and vascular diseases of the retina and choroid. Although anti-VEGF drugs have been used to effectively treat neovascularization, long-term use of anti-angiogenic factors can cause a variety of neurological and developmental side effects. As a result, better drugs to treat ocular neovascularization are urgently required. There is mounting evidence that epigenetic regulation is important in ocular neovascularization. DNA methylation and histone modification, non-coding RNA, and mRNA modification are all examples of epigenetic mechanisms. In order to shed new light on epigenetic therapeutics in ocular neovascularization, this review focuses on recent advances in the epigenetic control of ocular neovascularization as well as discusses these new mechanisms.

Influenza shares the same putative transmission pathway with coronavirus disease 2019 (COVID-19), and causes tremendous morbidity and mortality annually globally. Since the transmission of COVID-19 in China, a series of non-pharmaceutical interventions (NPIs) against to the disease have been implemented to contain its transmission. Based on the surveillance data of influenza, Search Engine Index, and meteorological factors from 2011 to 2021 in Xi'an, and the different level of emergence responses for COVID-19 from 2020 to 2021, Bayesian Structural Time Series model and interrupted time series analysis were applied to quantitatively assess the impact of NPIs in sequent phases with different intensities, and to estimate the reduction of influenza infections. From 2011 to 2021, a total of 197,528 confirmed cases of influenza were reported in Xi'an, and the incidence of influenza continuously increased from 2011 to 2019, especially, in 2019–2020, when the incidence was up to 975.90 per 100,000 persons; however, it showed a sharp reduction of 97.68% in 2020–2021, and of 87.22% in 2021, comparing with 2019–2020. The highest impact on reduction of influenza was observed in the phase of strict implementation of NPIs with an inclusion probability of 0.54. The weekly influenza incidence was reduced by 95.45%, and an approximate reduction of 210,100 (95% CI: 125,100–329,500) influenza infections was found during the post-COVID-19 period. The reduction exhibited significant variations in the geographical, population, and temporal distribution. Our findings demonstrated that NPIs against COVID-19 had a long-term impact on the reduction of influenza transmission.

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi'an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi'an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics.

Brucellosis is a chronic infectious disease caused by brucellae or other bacteria directly invading human body. Brucellosis presents the aggregation characteristics and periodic law of infectious diseases in temporal and spatial distribution. Taking major European countries as an example, this study established the temporal and spatial distribution sequence of brucellosis, analyzed the temporal and spatial distribution characteristics of brucellosis, and quantitatively predicted its epidemic law by using different traditional or machine learning models. This paper indicates that the epidemic of brucellosis in major European countries has statistical periodic characteristics, and in the same cycle, brucellosis has the characteristics of piecewise trend. Through the comparison of the prediction results of the three models, it is found that the prediction effect of long short-term memory and convolutional long short-term memory models is better than autoregressive integrated moving average model. The first mock exam using Conv layer and data vectorizations predicted that the convolutional long short-term memory model outperformed the traditional long short-term memory model. Compared with the monthly scale, the prediction of the trend stage of brucellosis can achieve better results under the single model prediction. These findings will help understand the development trend and liquidity characteristics of brucellosis, provide corresponding scientific basis and decision support for potential risk assessment and brucellosis epidemic prevention and control, and reduce the loss of life and property.

(1) Background: Tuberculosis (TB) is an infectious disease that seriously endangers health and restricts economic and social development. Shandong Province has the second largest population in China with a high TB burden. This study aimed to detect the epidemic characteristics and spatio-temporal pattern of reported TB incidence in Shandong Province and provide a scientific basis to develop more effective strategies for TB prevention and control. (2) Methods: The age, gender, and occupational distribution characteristics of the cases were described. The Seasonal-Trend LOESS decomposition method, global spatial autocorrelation statistic, local spatial autocorrelation statistics, and spatial-temporal scanning were used to decompose time series, analyze the spatial aggregation, detect cold and hot spots, and analyze the spatio-temporal aggregation of reported incidence. (3) Results: A total of 135,185 TB cases were reported in Shandong Province during the five years 2016–2020. Men and farmers are the main populations of TB patients. The time-series of reported tuberculosis incidence had a long-term decreasing trend with clear seasonality. There was aggregation in the spatial distribution, and the areas with a high reported incidence of TB were mainly clustered in the northwest and southeast of Shandong. The temporal scan also yielded similar results. (4) Conclusions: Health policy authorities should develop targeted prevention and control measures based on epidemiological characteristics to prevent and control TB more effectively.

Guangxi fermented bamboo shoots (GFBS) are widely appreciated by consumers in China because of their unique aroma. In this study, the dominant aroma compounds of GFBS were investigated using gas chromatography-olfactometry-mass spectrometry, odor-activity values, and aroma recombination. The results show that 70 aroma compounds, including alcohols, esters, aldehydes, acids, phenols, ethers, ketones, alkenes, benzene derivatives, and furans, were identified in GFBS. Among them, 15 aroma compounds with odor-activity values (OAVs) > 1 were identified. Aroma-recombination-omission experiments and sensory evaluation demonstrated that octanal, (E)-2-octenal, acetic acid, guaiacol, phenylethyl alcohol, creosol, 4-ethylguaiacol, and p-cresol significantly contributed to the characteristic aroma of GFBS. Most importantly, p-cresol (34,997.95 ≤ OAV ≤ 71,409.51) and acetic acid (2155.79 ≤ OAV ≤ 3872.09) significantly contributed to its aroma (p < 0.001). The major aroma profile of GFBS included a strong fermented odor, which was pungent and sour. This study provides a theoretical basis for improving the flavor of GFBS.

In the drilling industry, it is of great significance to accurately predict the drag coefficient and settling velocity of drill cuttings falling in the non-Newtonian drilling fluid. However, the irregular shape of drill cuttings and the non-Newtonian rheological properties of drilling fluid (e.g., shear-thinning and yield stress behavior) make it challenging to predict the settling velocity. In this study, the velocity of particle settlement was studied by a visual device and high-speed camera system. Experimental data of the free settlement of 224 irregular drilling cuttings and 105 spherical particles in the Herschel–Bulkley fluid were obtained. A mechanical model dependent on the force balance of settlement particles was adopted to conduct a detailed statistical analysis of the experimental results, and a prediction model of the drag coefficient of spherical particles in the Herschel–Bulkley fluid was established. A two-dimensional shape description parameter is introduced to establish a model for predicting the drag coefficient of irregular-shaped cuttings in a Herschel–Bulkley fluid. The model has high prediction accuracy for the settling velocity of irregular shale cuttings in Herschel–Bulkley fluid. The average relative error is 7.14%, verifying the model’s accuracy.

The celiac ganglion projects its postganglionic (including purinergic) fibers to the liver. P2Y12 receptor is one of the P2Y family members. We found that the expression levels of P2Y12 receptor in both celiac ganglia and liver were increased in type 2 diabetes mellitus (T2DM) rats which also displayed an enhanced activity of celiac sympathetic nerve discharge (SND). In addition, a marked decrease of hepatic glucokinase (GK) expression was accompanied by reduced hepatic glycogen synthesis in T2DM rats, whereas meanwhile the levels of NLRP3, active caspase-1, NF-κB, and interleukin-1β were elevated. All these abnormal alterations could be largely reversed after treatment of short hairpin RNA (shRNA) targeting P2Y12. Our results indicate that the silence of P2Y12 by shRNA may effectively correct the anomalous activity of celiac SND and improve the dysfunctional hepatic glucokinase by counteracting hepatocyte inflammation and likely pyroptosis due to activated NLRP3 inflammasome and caspase-1 signaling, thereby attenuating hyperglycemia in T2DM rats.

Maize vivipary, precocious seed germination on the ear, affects yield and seed quality. The application of multi-omics approaches, such as transcriptomics or metabolomics, to classic vivipary mutants can potentially reveal the underlying mechanism. Seven maize vivipary mutants were selected for transcriptomic and metabolomic analyses. A suite of transporters and transcription factors were found to be upregulated in all mutants, indicating that their functions are required during seed germination. Moreover, vivipary mutants exhibited a uniform expression pattern of genes related to abscisic acid (ABA) biosynthesis, gibberellin (GA) biosynthesis, and ABA core signaling. NCED4 (Zm00001d007876), which is involved in ABA biosynthesis, was markedly downregulated and GA3ox (Zm00001d039634) was upregulated in all vivipary mutants, indicating antagonism between these two phytohormones. The ABA core signaling components (PYL-ABI1-SnRK2-ABI3) were affected in most of the mutants, but the expression of these genes was not significantly different between the vp8 mutant and wild-type seeds. Metabolomics analysis integrated with co-expression network analysis identified unique metabolites, their corresponding pathways, and the gene networks affected by each individual mutation. Collectively, our multi-omics analyses characterized the transcriptional and metabolic landscape during vivipary, providing a valuable resource for improving seed quality.

We developed a model to describe polarized photon scattering in biological tissues. In this model, tissues are simplified to a mixture of scatterers and surrounding medium. There are two types of scatterers in the model: solid spheres and infinitely long solid cylinders. Variables related to the scatterers include: the densities and sizes of the spheres and cylinders, the orientation and angular distribution of cylinders. Variables related to the surrounding medium include: the refractive index, absorption coefficient and birefringence. In this paper, as a development we introduce an optical activity effect to the model. By comparing experiments and Monte Carlo simulations, we analyze the backscattering Mueller matrix patterns of several tissue-like media, and summarize the different effects coming from anisotropic scattering and optical properties. In addition, we propose a possible method to extract the optical activity values for tissues. Both the experimental and simulated results show that, by analyzing the Mueller matrix patterns, the microstructure and optical properties of the medium can be obtained. The characteristic features of Mueller matrix patterns are potentially powerful tools for studying the contrast mechanisms of polarization imaging for medical diagnosis.