Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.

The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3highPD-L1high super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8+ T cells in mice. These findings reveal the mechanism by which tumor-neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.

Miniaturized metachronal magnetic artificial cilia.

Biological cilia, hairlike organelles on cell surfaces, often exhibit collective wavelike motion known as metachrony, which helps generating fluid flow. Inspired by nature, researchers have developed artificial cilia as microfluidic actuators, exploring several methods to mimic the metachrony. However, reported methods are difficult to miniaturize because they require either control of individual cilia properties or the generation of a complex external magnetic field. We introduce a concept that generates metachronal motion of magnetic artificial cilia (MAC), even though the MAC are all identical, and the applied external magnetic field is uniform. This is achieved by integrating a paramagnetic substructure in the substrate underneath the MAC. Uniquely, we can create both symplectic and antiplectic metachrony by changing the relative positions of MAC and substructure. We demonstrate the flow generation of the two metachronal motions in both high and low Reynolds number conditions. Our research marks a significant milestone by breaking the size limitation barrier in metachronal artificial cilia. This achievement not only showcases the potential of nature-inspired engineering but also opens up a host of exciting opportunities for designing and optimizing microsystems with enhanced fluid manipulation capabilities.

TRIM21/USP15 balances ACSL4 stability and the imatinib resistance of gastrointestinal stromal tumors.

BACKGROUND: Imatinib has become an exceptionally effective targeted drug for treating gastrointestinal stromal tumors (GISTs). Despite its efficacy, the resistance to imatinib is common in GIST patients, posing a significant challenge to the effective treatment. METHODS: The expression profiling of TRIM21, USP15, and ACSL4 in GIST patients was evaluated using Western blot and immunohistochemistry. To silence gene expression, shRNA was utilized. Biological function of TRIM21, USP15, and ACSL4 was examined through various methods, including resistance index calculation, colony formation, shRNA interference, and xenograft mouse model. The molecular mechanism of TRIM21 and USP15 in GIST was determined by conducting Western blot, co-immunoprecipitation, and quantitative real-time PCR (qPCR) analyses. RESULTS: Here we demonstrated that downregulation of ACSL4 is associated with imatinib (IM) resistance in GIST. Moreover, clinical data showed that higher levels of ACSL4 expression are positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that the reduced expression of ACSL4 in GIST is attributed to excessive protein degradation mediated by the E3 ligase TRIM21 and the deubiquitinase USP15. CONCLUSION: These findings demonstrate that the TRIM21 and USP15 control ACSL4 stability to maintain the IM sensitive/resistant status of GIST.

Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression.

BACKGROUND: Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells and mainly leads to but is not limited to its apoptosis and autophagy. Ferroptosis has been also reported to participate, while little is known about it. Our previous experiment has demonstrated that endometrial stem cells (EnSCs) can repair cisplatin-injured granulosa cells. However, it is still unclear whether EnSCs can play a repair role by acting on ferroptosis. METHODS: Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied to detect the expression levels of ferroptosis-related genes. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell viability. Transmission electron microscopy (TEM) was performed to detect ferroptosis in morphology. And the extent of ferroptosis was assessed by ROS, GPx, GSSG and MDA indicators. In vivo, ovarian morphology was presented by HE staining and the protein expression in ovarian tissue was detected by immunohistochemistry. RESULTS: Our results showed that ferroptosis could occur in cisplatin-injured granulosa cells. Ferroptosis inhibitor ferrostatin-1 (Fer-1) and EnSCs partly restored cell viability and mitigated the damage of cisplatin to granulosa cells by inhibiting ferroptosis. Moreover, the repair potential of EnSCs can be markedly blocked by ML385. CONCLUSION: Our study demonstrated that cisplatin could induce ferroptosis in granulosa cells, while EnSCs could inhibit ferroptosis and thus exert repair effects on the cisplatin-induced injury model both in vivo and in vitro. Meanwhile, Nrf2 was validated to participate in this regulatory process and played an essential role.

Characterization of the prognostic, diagnostic, and immunological roles of DSCC1 and its genomic alteration and instability in human cancers.

DNA replication and sister chromatid cohesion 1 (DSCC1) exerts various functions including sister chromatid cohesion. DSCC1 overexpression plays an important role in cancer development, such as in colorectal, breast, and hepatocellular cancers. The specific role of DSCC1 in tumor progression remains largely unknown, necessitating a pan-cancer investigation to understand the potential function of DSCC1 in various cancers. In this study, we obtained data on physiological conditions, transcriptional expression, survival prognosis, genomic alteration, genomic instability, enriched pathways, immune infiltration, and immunotherapy from The Cancer Genome Atlas, The Genotype-Tissue Expression, cBioPortal, and other publicly available databases to systematically characterize the oncogenic and immunological roles of DSCC1 in 33 different cancers. We found that DSCC1 expression was upregulated at both mRNA and protein levels in various cancers. Additionally, DSCC1 expression was associated with higher tumor stage and grade in specific cancers. DSCC1 was a potential pan-cancer prognostic biomarker for its close association with patient prognosis and a diagnostic biomarker for its high predictive value in distinguishing tumor tissues from normal tissues. DSCC1 was universally amplified across different cancers and tightly associated with genomic instability. Moreover, DSCC1 had a close relationship with tumor immune cell infiltration; thus, it could be used as a potential biomarker for predicting the response and survival of patients with cancer who receive immune checkpoint blockade treatment. To sum up, our study revealed that DSCC1 is a promising target for tumor therapy.

Description and reconstruction of typical structured light beams with vector spherical wave functions.

It is well known that the generalized Lorenz-Mie theory (GLMT) is a rigorous analytical method for dealing with the interaction between light beams and spherical particles, which involves the description and reconstruction of the light beams with vector spherical wave functions (VSWFs). In this paper, a detailed study on the description and reconstruction of the typical structured light beams with VSWFs is reported. We first systematically derive the so-called beam shape coefficients (BSCs) of typical structured light beams, including the fundamental Gaussian beam, Hermite-Gaussian beam, Laguerre-Gaussian beam, Bessel beam, and Airy beam, with the aid of the angular spectrum decomposition method. Then based on the derived BSCs, we reconstruct these structured light beams using VSWFs and compare the results of the reconstructed beams with those of the original beams. Our results will be useful in the study of the interaction of typical structured light beams with spherical particles in the framework of GLMT.

Role of single-cell ferroptosis regulation in intercellular communication and skin cutaneous melanoma progression and immunotherapy.

BACKGROUND: The involvement of ferroptosis in the pathogenesis and progression of various cancers has been well established. However, limited studies have investigated the role of ferroptosis-mediated tumor microenvironment (TME) in skin cutaneous melanoma (SKCM). METHODS: By leveraging single-cell RNA sequencing data, the nonnegative matrix factorization (NMF) approach was employed to comprehensively characterize and identify distinct gene signatures within ferroptosis-associated TME cell clusters. Prognostic and treatment response analyses were conducted using both bulk datasets and external cancer cohort to evaluate the clinical implications of TME clusters. RESULTS: This NMF-based analysis successfully delineated fibroblasts, macrophages, T cells, and B cells into multiple clusters, enabling the identification of unique gene expression patterns and the annotation of distinct TME clusters. Furthermore, pseudotime trajectories, enrichment analysis, cellular communication analysis, and gene regulatory network analysis collectively demonstrated significant intercellular communication between key TME cell clusters, thereby influencing tumor cell development through diverse mechanisms. Importantly, our bulk RNA-seq analysis revealed the prognostic significance of ferroptosis-mediated TME cell clusters in SKCM patients. Moreover, our analysis of immune checkpoint blockade highlighted the crucial role of TME cell clusters in tumor immunotherapy, facilitating the discovery of potential immunotherapeutic targets. CONCLUSIONS: In conclusion, this pioneering study employing NMF-based analysis unravels the intricate cellular communication mediated by ferroptosis within the TME and its profound implications for the pathogenesis and progression of SKCM. We provide compelling evidence for the prognostic value of ferroptosis-regulated TME cell clusters in SKCM, as well as their potential as targets for immunotherapy.

Influence of temperature and humidity on scattering characteristics of aerosol particles in the terahertz band.

The terahertz band is considered to be the next breakthrough point to revolutionize communication technology, attributed to its rich spectrum resources. The study of terahertz atmospheric transmission characteristics is important in guiding the terahertz communication window selection process. In this report, based on the equivalent medium theory, the scattering characteristics of terahertz Gaussian beams by moist media are discussed. Numerical results show that the extinction coefficient of particles is mainly affected by the humidity, and the scattering efficiency is affected by both temperature and humidity. When the temperature is over 273 K and the humidity is 0.5, the extinction efficiency shows a trend of increasing initially and decreasing afterwards. Hence, the appropriate temperature is beneficial to minimizing the attenuation coefficient.

Reflection and refraction of higher-order Hermite-Gaussian beams: a vector wave analysis.

Hermite-Gaussian beams, as a typical kind of higher-order mode laser beams, have attracted intensive attention because of their interesting properties and potential applications. In this paper, a full vector wave analysis of the higher-order Hermite-Gaussian beams upon reflection and refraction is reported. The explicit analytical expressions for the electric and magnetic field components of the reflected and refracted Hermite-Gaussian beams are derived with the aid of angular spectrum representation and vector potential in the Lorenz gauge. Based on the derived analytical expressions, local field distributions of higher-order Hermite-Gaussian beams reflection and refraction at a plane interface between air and BK7 glass are displayed and analyzed.

Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy.

BACKGROUND: Although WD repeat and high-mobility group box DNA binding protein 1 (WDHD1) played an essential role in DNA replication, chromosome stability, and DNA damage repair, the panoramic picture of WDHD1 in human tumors remains unclear. Hence, this study aims to comprehensively characterize WDHD1 across 33 human cancers. METHODS: Based on publicly available databases such as TCGA, GTEx, and HPA, we used a bioinformatics approach to systematically explore the genomic features and biological functions of WDHD1 in pan-cancer. RESULTS: WDHD1 mRNA levels were significantly increased in more than 20 types of tumor tissues. Elevated WDHD1 expression was associated with significantly shorter overall survival (OS) in 10 tumors. Furthermore, in uterine corpus endometrial carcinoma (UCEC) and liver hepatocellular carcinoma (LIHC), WDHD1 expression was significantly associated with higher histological grades and pathological stages. In addition, WDHD1 had a high diagnostic value among 16 tumors (area under the ROC curve [AUC] > 0.9). Functional enrichment analyses suggested that WDHD1 probably participated in many oncogenic pathways such as E2F and MYC targets (false discovery rate [FDR] < 0.05), and it was involved in the processes of DNA replication and DNA damage repair (p.adjust < 0.05). WDHD1 expression also correlated with the half-maximal inhibitory concentrations (IC50) of rapamycin (4 out of 10 cancers) and paclitaxel (10 out of 10 cancers). Overall, WDHD1 was negatively associated with immune cell infiltration and might promote tumor immune escape. Our analysis of genomic alterations suggested that WDHD1 was altered in 1.5% of pan-cancer cohorts and the "mutation" was the predominant type of alteration. Finally, through correlation analysis, we found that WDHD1 might be closely associated with tumor heterogeneity, tumor stemness, mismatch repair (MMR), and RNA methylation modification, which were all processes associated with the tumor progression. CONCLUSIONS: Our pan-cancer analysis of WDHD1 provides valuable insights into the genomic characterization and biological functions of WDHD1 in human cancers and offers some theoretical support for the future use of WDHD1-targeted therapies, immunotherapies, and chemotherapeutic combinations for the management of tumors.

Research on Traffic Flow Prediction at Intersections Based on DT-TCN-Attention.

Traditional nonintelligent signal control systems are typically used in road traffic signal systems, which cannot provide optimal guidance and have low traffic efficiency during rush hour. This study proposes a traffic signal phase dynamic timing optimization strategy based on a time convolution network and attention mechanism to improve traffic efficiency at intersections. The corresponding optimization was performed after predicting traffic conditions with different impacts using the digital twinning technique. This method uses a time-convolution network to extract the cross-time nonlinear characteristics of traffic data at road intersections. An attention mechanism was introduced to capture the relationship between the importance distribution and duration of the historical time series to predict the traffic flow at an intersection. The interpretability and prediction accuracy of the model was effectively improved. The model was tested using traffic flow data from a signalized intersection in Shangrao, Jiangxi Province, China. The experimental results indicate that the model generated by training has a strong learning ability for the temporal characteristics of traffic flow. The model has high prediction accuracy, good optimization results, and wide application prospects in different scenarios.

FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway.

Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2.

Polarization and coherence properties in self-healing propagation of a partially coherent radially polarized twisted beam.

With the help of generalized Huygens-Fresnel integral, an analytical expression for the self-healing of a partially coherent radially polarized twisted (PCRPT) beam is derived. The coherence and polarization properties of the PCRPT beam in self-healing propagation are studied in detail. It shows that the existence of the twist phase is a double-edged sword for the self-healing properties of the beam. With the increase of the twist factor, the self-healing ability of beam intensity distribution decreases. However, the anti-disturbance performance of beam polarization improves at the same time. Besides, the polarization and coherence distribution of the beam are proved that own a slight self-healing ability when the obstacle is small. Our results will be helpful to the fields of optical tweezers, microscopy, optical communication, and so on.

Chirality of optical vortex beams reflected from an air-chiral medium interface.

Chirality plays an important role in understanding of the chiral light-matter interaction. In this work, we study theoretically and numerically the chirality of optical vortex beams reflected from an air-chiral medium interface. A theoretical model that takes into full account the vectorial nature of electromagnetic fields is developed to describe the reflection of optical vortex beams at an interface between air and a chiral medium. Some numerical simulations are performed and discussed. The results show that the chirality of the reflected vortex beams can be well controlled by the relative chiral parameter of the medium and is significantly affected by the incidence angle, topological charge, and polarization state of the incident beam. Our results provide new, to the best of our knowledge, insights into the interactions between optical vortex beams with chiral matter, and may have potential application in optical chirality manipulation.

Concise and explicit expressions for typical spatial-structured light beams beyond the paraxial approximation.

Structured light beams with distinct spatial inhomogeneity of amplitude, phase, and polarization have garnered tremendous attention in recent years. A better understanding of the vectorial structure of such beams is helpful to reveal their important and interesting features for further applications. In this paper, explicit analytical expressions for the electric field components of typical spatial-structured light beams, including fundamental Gaussian beams, Hermite-Gaussian beams, Laguerre-Gaussian beams, Bessel/Bessel-Gaussian beams, and Airy beams, beyond the paraxial approximation are derived on the basis of the vectorial Rayleigh-Sommerfeld diffraction integrals. Compared with the existing expressions in the literature, the expressions given in this paper are very concise. Using the derived analytical expressions, distributions of the electric field components of these typical structured light beams are displayed and analyzed.

Implementation of typical structured light beams in discrete dipole approximation for scattering problems.

In this work, we report an implementation of typical structured light beams, including the Hermite-Gaussian beams, Laguerre-Gaussian beams, Bessel beams, and Airy beams, in the discrete dipole approximation (DDA) for scattering problems of small particles. The analytical expressions for the electric field components of these beams are presented, and the detailed processes for the implementation of these beams in DDA are given, with particular emphasis on the explicit codes. The calculated result for our codes of Gaussian beams is compared with that from the Amsterdam DDA codes, and very good agreement is observed. The internal and near-surface fields of a sphere illuminated by the typical structured light beams with different beam parameters are illustrated and discussed. Also, the intensity distributions of internal and near-surface fields as well as the scattering efficiency factor for the scattering of structured light beams as mentioned above by sphere, spheroid, and cylinder are presented. The proposed codes can be directly used for the investigation of scattering of typical structured light beams by complex particles within the framework of the DDA.

Scattering analysis of two-dimensional Airy beams by typical non-spherical particles.

The scattering of structured light beams by various particles is an important subject of research with myriad practical applications, such as the manipulation, measurement, and diagnosis of small particles. We carry out an analysis of the scattering of two-dimensional (2D) Airy beams by typical non-spherical particles. The electric and magnetic field vectors of the incident Airy beams are derived by introducing a vector potential in the Lorenz gauge. The scattered fields of the particles are obtained by utilizing the method of moments based on surface integral equations. Some numerical simulations for the scattering of 2D Airy beams by several selected non-spherical particles are performed and analyzed. Especially, a spheroidal particle is taken as an example, and the effects of various parameters describing the 2D Airy beams on its differential scattering cross section are examined. It is expected that this work will be helpful for understanding the interactions of 2D Airy beams with non-spherical particles and their further applications.

How does COVID-19 pandemic impact cities' logistics performance? An evidence from China's highway freight transport.

The pandemic COVID-19 which has spread over the world in early 2020 has caused significant impacts not only on health and life, but also on production activities and freight work. However, few studies were about the effect of COVID-19 on the performance of cities' logistics. Hence, this study focuses on the Belt and Road Initiative (BRI) and compares the changes in logistics performance from a spatial perspective caused by COVID-19 that are reflected on the highway freight between its 18 node cities in 2019 and 2020 of the same periods for 72 days. This study uses the entropy weight method to reflect the impact that COVID-19 has caused to the logistics level. Based on the modified gravity model, the impact on the logistics spatial connection between node cities was analyzed. These two aspects have been combined to analyze the logistics performance. The results show that the node cities have been affected by COVID-19 dissimilarly, and the impact has regional characteristics. The logistics level and spatial connection of Wuhan are the most seriously declined. The decline in logistics level has the same spatial variation law as the confirmed cases. The logistics connection between Wuhan and the surrounding node cities and the three-node cities in the northeast of China are also severely affected by the pandemic because of the expressway control policies. The regional distribution of logistics performance has differences, and the correlation of the logistics level and logistics spatial connection decreases. Besides, this study puts forward different recovery suggestions and policies for different belts in the BRI, such as focusing on restoring areas and giving full play to the role of the Chengdu-Chongqing urban agglomeration and logistics corridor. Finally, further provides corresponding suggestions for reducing the impact of emergencies from the perspectives of logistics hubs.

Will multi-industry supply chains' resilience under the impact of COVID-19 pandemic be different? A perspective from China's highway freight transport.

The pandemic caused by coronavirus disease 2019(COVID-19) continues to disrupt the global supply chain system, bringing new risks and challenges. The uncertainty created by COVID-19 makes it is difficult for various industries to deal with the pandemic. Since the pandemic, the supply chain's resilience has been discussed and examined in some studies. However, most existing works start from a single industry perspective or pay more attention to the disturbance caused by changes in the production side. Supply chain networks of different industries, mainly transport networks, are relatively limited under the epidemic's impact. In this paper, from the perspective of highway freight transport, a comprehensive competitiveness evaluation framework was proposed to reveal and the disruption and resilience of the supply chain under the outbreak based on nine indexes with five dimensions, including efficiency, capacity, activity, connectivity, and negotiability. Based on the availability of the data(Large-scale truck trajectory), we sorted out seven categories of Chinese industries(related to highway transport) and divided them into four categories respectively: (a) Slight disruption and worse resilience; (b) Slight disruption and remarkable resilience; (c) Serious disruption and worse resilience; (d) Serious disruption and remarkable resilience. The measurement results of supply chain network performance show that the industries (cold-chain, general products, and other industries) dominated by "Efficiency - Negotiability - Connectivity" are slightly disrupted (about 33%), forming a spatial diffusion with Wuhan(the city where the pandemic first broke out) as the disrupted center, spreading outward in a circle structure. Simultaneously, five urban agglomerations surrounding it have been impacted. By contrast, due to the strict isolation measures, the industries (building materials, construction, engineering, and high-value products industry) more vulnerable to be disrupted seriously (about 82%) tend to be the pattern of "Capacity - Activity". However, a large-scale centralized disruption was observed in the Triangle of Central China urban agglomeration was presented, resulting in almost stagnation of industry development. Meanwhile, as the future of the pandemic remains uncertain, the supply chain represented by the engineering industry, construction industry, etc are deserved to be paid more attention in line with they are prone to large-scale centralized damage due to the disruption of a single city node.

Light scattering of Laguerre-Gaussian vortex beams by arbitrarily shaped chiral particles.

Laguerre-Gaussian (LG) beams with vortex phase possess a handedness, which would produce chiroptical interactions with chiral matter and may be used to probe structural chirality of matter. In this paper, we numerically investigate the light scattering of LG vortex beams by chiral particles. Using the vector potential method, the electric and magnetic field components of the incident LG vortex beams are derived. The method of moments (MoM) based on surface integral equations (SIEs) is applied to solve the scattering problems involving arbitrarily shaped chiral particles. The numerical results for the differential scattering cross sections (DSCSs) of several selected chiral particles illuminated by LG vortex beams are presented and analyzed. In particular, we show how the DSCSs depend on the chiral parameter of the particles and on the parameters describing the incident LG vortex beams, including the topological charge, the state of circular polarization, and the beam waist. This research may provide useful insights into the interaction of vortex beams with chiral particles and its further applications.