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Abstract Background A growing body of evidence indicates that histone variants play an oncogenic role in cancer progression. However, the role and mechanism of histone variant H2AZ1 in lung cancer remain poorly understood. In this study, we aim to identify novel functions and molecular mechanisms of H2AZ1 in lung cancer. Methods We analyzed H2AZ1 expression in lung adenocarcinoma using several RNA-seq and microarray datasets. Immunohistochemistry staining for H2AZ1 was performed on two sets of lung cancer tissue microarrays. To study the function of H2AZ1, we conducted assays for cell proliferation, colony formation, invasion, and migration. We employed CUT&Tag-seq, ATAC-seq, RNA-seq, and Western blotting to explore the regulatory patterns and potential mechanisms of H2AZ1 in lung adenocarcinoma. Results Our findings reveal that H2AZ1 is highly expressed in lung cancer and high levels of H2AZ1 mRNA are associated with poor patient survival. Silencing H2AZ1 impaired cell proliferation, colony formation, migration, and invasion. Mechanistically, our CUT&Tag-seq, ATAC-seq, and RNA-seq results showed that H2AZ1 is primarily deposited around TSS and affects multiple oncogenic signaling pathways. Importantly, we uncovered that H2AZ1 may drive lung cancer progression through the RELA-HIF1A-EGFR signaling pathway. Conclusion H2AZ1 plays an oncogenic role via several cancer-related pathways, including the RELA-HIF1A-EGFR axis in lung cancer. Intervention targeting H2AZ1 and its related signaling genes may have translational potential for precision therapy.

Abstract Ruthenium (Ru) has been recognized as a prospective candidate to substitute platinum catalysts in water‐splitting‐based hydrogen production. However, minimizing the Ru contents, optimizing the water dissociation energy of Ru sites, and enhancing the long‐term stability are extremely required, but still face a great challenge. Here, we report on creating tungsten oxide‐anchored Ru clusters (Ru–WOx) with electron‐rich and anti‐corrosive microenvironments for efficient and robust seawater splitting. Benefiting from the abundant oxygen vacancy structure in tungsten oxide support, the Ru–WOx exhibits strong Ru–O and Ru–W bonds at the interface. Our study elucidates that the strong Ru–O bonds in Ru–WOx may accelerate the water dissociation kinetics, and the Ru–W bonds will lead to the strong metal–support interaction and electrons transfer from W to Ru. The optimal Ru–WOx catalysts exhibit a low overpotential of 29 and 218 mV at the current density of 10 mA cm−2 in alkaline and seawater media, respectively. The outstanding long‐term stability discloses that the Ru–WOx catalysts own efficient corrosion resistance in seawater electrolysis. We believe that this work offers new insights into the essential roles of electron‐rich and anti‐corrosive microenvironments in Ru‐based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.

Abstract Background TFE3 immunohistochemistry (TFE3‐IHC) is controversial in the diagnosis of TFE3‐rearranged renal cell carcinoma (TFE3‐rearranged RCC). This study is to investigate the accuracy and sensitivity of IHC and establish a predictive model to diagnose TFE3‐rearranged RCC. Methods Retrospective analysis was performed by collecting IHC and fluorescence in situ hybridization (FISH) results from 228 patients. IHC results were evaluated using three scoring systems. Scoring system 1 is graded based on nuclear staining intensity, scoring system 2 is graded based on the percentage of stained tumor cell nuclei, and scoring system 3 is graded based on both the nuclear staining intensity and the percentage. We collected patients' IHC results and clinical information. Important variables were screened based on univariate logistic regression analysis. Then, independent risk factors were established through multivariate logistic regression, and a nomogram model was constructed. The model was validated in internal test set and external validation set. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) were generated to assess discriminative ability of the model. Results The accuracy of IHC based on three scoring systems were 0.829, 0.772, and 0.807, respectively. The model included four factors including age, gender, lymph node metastasis and IHC results. Area under the curve (AUC) values were 0.935 for the training set, 0.934 for the internal test set, 0.933 for all 228 patients, and 0.916 for the external validation set. Conclusions TFE3 IHC has high accuracy in the diagnosis of TFE3‐rearranged RCC. Clinical information such as age and lymph node metastasis are independent risk factors, which can be used as a supplement to the results of TFE3 IHC. This study confirms the value of IHC in the diagnosis of TFE3‐rearranged RCC. The accuracy of the diagnosis can be improved by incorporating IHC with other clinical risk factors.

Although numerous photothermal nanoparticles have been designed to improve the enhanced and permeability and retention (EPR) effect, the delivery of nanoparticles to the tumor site remains a major obstacle in cancer treatment. The interstital structure and its internal fluid that play an important role in material transmission, intercellular signal transduction, tissue morphology, immunity, tumor development, and disease diagnosis and treatment may be considered as a new route for drug delivery. Here, we prepared a nanoplatform composed of polydopamine (PDA), indocyanine green (ICG) as a photothermal agent, and paclitaxel (PTX) as a chemotherapeutic drug. The designed PDA-ICG nanoparticles displayed excellent photothermal conversion ability, with the synergistic effect of PTX, the growth of MDA-MB-231 cells was significantly suppressed with the cell viability of 6.19% in vitro. Taking advantage of bioimaging ability of ICG, tumor-targeting of the nanoparticles injected into the interstitial space was study, Compared with intravenous injection, nanoparticles better targeted the tumor based on the interstitial fluid flow in MBA-MD-231 bearing mice. Furthermore, the antitumor efficacy was studied in vivo. With the improved accumulation of PDA-ICG-PTX nanoparticles injected into the interstitial space and the synergistic effect of photothermal therapy and chemotherapy, tumor growth was inhibited without obvious side effects. These results demonstrated that interstitial space injection may be a superior administration route for tumor-targeting nanoparticles. The PDA-ICG-PTX nanoparticles delivered via the interstitial space exhibit great potential in the photothermal chemotherapy of cancers.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is a highly invasive and metastatic subtype of kidney malignancy and is correlated with metabolic reprogramming for adaptation to the tumor microenvironment comprising infiltrated immune cells and immunomodulatory molecules. The role of immune cells in the tumor microenvironment (TME) and their association with abnormal fatty acids metabolism in ccRCC remains poorly understood. Method RNA-seq and clinical data of KIRC from The Cancer Genome Atlas (TCGA) and E-MTAB-1980 from the ArrayExpress dataset. The Nivolumab group and Everolimus group of the CheckMate 025 study, the Atezolizumab arm of IMmotion150 and the Atezolizumab plus Bevacizumab group of IMmotion151 cohort were obtained for subsequent analysis. After differential expression genes identification, the signature was constructed through univariate Cox proportional hazard regression and simultaneously the least absolute shrinkage and selection operator (Lasso) analysis and the predictive performance of our signature was assessed by using receiver operating characteristic (ROC), Kaplan–Meier (KM) survival analysis, nomogram, drug sensitivity analysis, immunotherapeutic effect analysis and enrichment analysis. Immunohistochemistry (IHC), qPCR and western blot were performed to measure related mRNA or protein expression. Biological features were evaluated by wound healing, cell migration and invasion assays and colony formation test and analyzed using coculture assay and flow cytometry. Results Twenty fatty acids metabolism-related mRNA signatures were constructed in TCGA and possessed a strong predictive performance demonstrated through time-dependent ROC and KM survival analysis. Notably, the high-risk group exhibited an impaired response to anti-PD-1/PD-L1 (Programmed death-1 receptor/Programmed death-1 receptor-ligand) therapy compared to the low-risk group. The overall levels of the immune score were higher in the high-risk group. Additionally, drug sensitivity analysis observed that the model could effectively predict efficacy and sensitivity to chemotherapy. Enrichment analysis revealed that the IL6-JAK-STAT3 signaling pathway was a major pathway. IL4I1 could promote ccRCC cells’ malignant features through JAK1/STAT3 signaling pathway and M2-like macrophage polarization. Conclusion The study elucidates that targeting fatty acids metabolism can affect the therapeutic effect of PD-1/PD-L1 in TME and related signal pathways. The model can effectively predict the response to several treatment options, underscoring its potential clinical utility.

A suspended dense graded broken stone road foundation stabilized by cement is a commonly employed material in roadworks, which is vulnerable to harm caused by freezing and thawing processes. This investigation intends to evaluate the laboratory behavior and the characteristics of freezing and thawing process-induced deterioration in a broken stone road foundation stabilized by cement with suspended dense grading, employing mechanical examinations and acoustical methods. The rate of mass loss in the broken stone road foundation stabilized by cement progressively rises, and the rate of decline in the compressive strength could potentially intensify as freezing and thawing processes augment. The modulus of resilience diminishes as freezing and thawing processes progress, and ultrasonic wave velocity also decreases. The patterns of mass loss, compressive strength decline, resilience modulus reduction, and ultrasonic wave velocity alteration adhere to a parabolic fitting relationship with freeze–thaw cycles, with an R2 above 0.95. The curves depicting the relationship of mass, compressive strength, resilience modulus, and ultrasonic wave velocity exhibit a steeper trend significantly after 10–15 cycles, which can be ascribed to the emergence of microcracks and the progression of flaws within the material. The evolution of damage in the broken stone road foundation stabilized by cement is monitored to progress through three distinct stages based on acoustic emission: initial, stationary, and failure. As freezing and thawing processes accumulate to 20 cycles, the length of initial phase correspondingly rises to three times, the length of failure stage diminishes to about one fifth.

Background Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms underlying the effect of LRFN2 on the tumor microenvironment (TME) and immunotherapy remain unclear.Methods Here we combined bulk RNA sequencing, single-cell RNA sequencing, ProcartaPlex multiple immunoassays, functional experiments, and TissueFAXS panoramic tissue quantification assays to demonstrate that LRFN2 shapes a non-inflammatory TME in BLCA.Results First, comprehensive multiomics analysis identified LRFN2 as a novel immunosuppressive target specific to BLCA. We found that tumor-intrinsic LRFN2 inhibited the recruitment and functional transition of CD8+ T cells by reducing the secretion of pro-inflammatory cytokines and chemokines, and this mechanism was verified in vitro and in vivo. LRFN2 restrained antitumor immunity by inhibiting the infiltration, proliferation, and differentiation of CD8+ T cells in vitro. Furthermore, a spatial exclusivity relationship was observed between LRFN2+ tumor cells and CD8+ T cells and cell markers programmed cell death-1 (PD-1) and T cell factor 1 (TCF-1). Preclinically, LRFN2 knockdown significantly enhanced the efficacy of ICI therapy. Clinically, LRFN2 can predict immunotherapy responses in real-world and public immunotherapy cohorts. Our results reveal a new role for LRFN2 in tumor immune evasion by regulating chemokine secretion and inhibiting CD8+ T-cell recruitment and functional transition.Conclusions Thus, LRFN2 represents a new target that can be combined with ICIs to provide a potential treatment option for BLCA.

Abstract Background The incidence of renal cell carcinoma (RCC) has increased in recent years. Metastatic RCC is common and remains a major cause of mortality. A regulatory role for circular RNAs (circRNAs) in the occurrence and progression of RCC has been identified, but their function, molecular mechanisms, and potential clinical applications remain poorly understood. Methods High‐throughput RNA sequencing was used to explore the differential expression of circRNAs and their related pathways in RCC patients. Transwell and CCK‐8 assays were used to assess the function of hsa_circ_0057105 in RCC cells. The clinical relevance of hsa_circ_0057105 was evaluated in a cohort of RCC patients. The hsa_circ_0057105 regulatory axis was defined using RNA pull‐down, luciferase reporter assays, and fluorescence in situ hybridization assays, and the in vivo effect of hsa_circ_0057105 was validated using animal experiments. Results Single‐sample gene set enrichment analysis and correlation analysis of RNA‐seq data showed that hsa_circ_0057105 was potentially oncogenic and may serve to regulate epithelial‐mesenchymal transition (EMT) activation in RCC. Hsa_circ_0057105 expression was associated with advanced TNM stages and was an independent prognostic factor for poor RCC patient survival. Phenotypic studies show that hsa_circ_0057105 can enhance the migration and invasion abilities of RCC cells. Further, hsa_circ_0057105 was shown to inhibit the expression of miR‐577, a miRNA that regulated the expression of both COL1A1, which induced EMT activation, and VDAC2, which modulated ferroptosis sensitivity. The dual regulatory roles of hsa_circ_0057105 on EMT and ferroptosis sensitivity were verified using rescue experiments. Animal studies confirmed that hsa_circ_0057105 increased the metastatic ability and ferroptosis sensitivity of RCC cells in vivo. Conclusions In RCC, hsa_circ_0057105 regulates COL1A1 and VDAC2 expression through its sponge effect on miR‐577, acting like a ‘double‐edged sword’. These findings provide new insight into the relationship between EMT and ferroptosis in RCC and provide potential biomarkers for RCC surveillance and treatment.

Abstract High lymphocyte infiltration and immunosuppression characterize the tumor microenvironment (TME) in renal cell carcinoma (RCC). There is an urgent need to elucidate how tumor cells escape the immune attack and to develop novel therapeutic targets to enhance the efficacy of immune checkpoint blockade (ICB) in RCC. Overactivated IFN‐γ‐induced JAK/STAT signaling involves in such TME, but the underlying mechanisms remain elusive. Here, EH domain‐binding protein 1‐like protein 1 (EHBP1L1) is identified as a crucial mediator of IFN‐γ/JAK1/STAT1/PD‐L1 signaling in RCC. EHBP1L1 is highly expressed in RCC, and high EHBP1L1 expression levels are correlated with poor prognosis and resistance to ICB. EHBP1L1 depletion significantly inhibits tumor growth, which is attributed to enhanced CD8+ T cell‐mediated antitumor immunity. Mechanistically, EHBP1L1 interacts with and stabilizes JAK1. By competing with SOCS1, EHBP1L1 protects JAK1 from proteasomal degradation, which leads to elevated JAK1 protein levels and JAK1/STAT1/PD‐L1 signaling activity, thereby forming an immunosuppressive TME. Furthermore, the combination of EHBP1L1 inhibition and ICB reprograms the immunosuppressive TME and prevents tumor immune evasion, thus significantly reinforcing the therapeutic efficacy of ICB in RCC patient‐derived xenograft (PDX) models. These findings reveal the vital role of EHBP1L1 in immune evasion in RCC, which may be a potential complement for ICB therapy.

Abstract Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.

Abstract Coronavirus disease 2019 continues to spread worldwide. Given the urgent need for effective treatments, many clinical trials are ongoing through repurposing approved drugs. However, clinical data regarding the cardiotoxicity of these drugs are limited. Human pluripotent stem cell‐derived cardiomyocytes (hCMs) represent a powerful tool for assessing drug‐induced cardiotoxicity. Here, by using hCMs, it is demonstrated that four antiviral drugs, namely, apilimod, remdesivir, ritonavir, and lopinavir, exhibit cardiotoxicity in terms of inducing cell death, sarcomere disarray, and dysregulation of calcium handling and contraction, at clinically relevant concentrations. Human engineered heart tissue (hEHT) model is used to further evaluate the cardiotoxic effects of these drugs and it is found that they weaken hEHT contractile function. RNA‐seq analysis reveals that the expression of genes that regulate cardiomyocyte function, such as sarcomere organization (TNNT2, MYH6) and ion homeostasis (ATP2A2, HCN4), is significantly altered after drug treatments. Using high‐throughput screening of approved drugs, it is found that ceftiofur hydrochloride, astaxanthin, and quetiapine fumarate can ameliorate the cardiotoxicity of remdesivir, with astaxanthin being the most prominent one. These results warrant caution and careful monitoring when prescribing these therapies in patients and provide drug candidates to limit remdesivir‐induced cardiotoxicity.

Purpose – The causes of high-speed railway failures are complex, and it is difficult to quantitatively and accurately describe safety evaluation. The purpose of this paper is to construct a model to ensure the safety of high-speed railway operations. Design/methodology/approach – The authors construct a high-speed railway operation safety evaluation index system from four aspects: personnel, equipment, environment and management and analyze the inter-coupling relationship of various safety factors. Based on the evaluation index system, the use of network analytic hierarchy process (ANP) and fuzzy comprehensive evaluation will be used to establish a high-speed railway operation safety evaluation model. Findings – Through the literature investigation and field investigation, combined with high-speed railway safety key points and system composition, 4 first-level indicators and 17 second-level indicators were selected to construct a high-speed railway operation safety evaluation index system. It can be seen from the results that the personnel management system and the signal and control system have the largest weight. Originality/value – On the basis of establishing an evaluation index system, comprehensively considering the internal coupling relationship between evaluation indexes and the fuzziness of high-speed railway operation safety evaluation, high-speed railway uses ANP fuzzy network analysis method to construct high-speed railway operation, and the safety evaluation model has certain advantages and practicability in the case of the relative lack of high-speed railway operation data and fault data.

Purpose – The operation safety of the high-speed railway has been widely concerned. Due to the joint influence of the environment, equipment, personnel and other factors, accidents are inevitable in the operation process. However, few studies focused on identifying contributing factors affecting the severity of high-speed railway accidents because of the difficulty in obtaining field data. This study aims to investigate the impact factors affecting the severity of the general high-speed railway. Design/methodology/approach – A total of 14 potential factors were examined from 475 data. The severity level is categorized into four levels by delay time and the number of subsequent trains that are affected by the accident. The partial proportional odds model was constructed to relax the constraint of the parallel line assumption. Findings – The results show that 10 factors are found to significantly affect accident severity. Moreover, the factors including automation train protection (ATP) system fault, platform screen door and train door fault, traction converter fault and railway clearance intrusion by objects have an effect on reducing the severity level. On the contrary, the accidents caused by objects hanging on the catenary, pantograph fault, passenger misconducting or sudden illness, personnel intrusion of railway clearance, driving on heavy rain or snow and train collision against objects tend to be more severe. Originality/value – The research results are very useful for mitigating the consequences of high-speed rail accidents.

Background Understanding the transmission source, pattern, and mechanism of infectious diseases is essential for targeted prevention and control. Though it has been studied for many years, the detailed transmission patterns and drivers for the seasonal influenza epidemics in China remain elusive. Methods In this study, utilizing a suite of epidemiological and genetic approaches, we analyzed the updated province-level weekly influenza surveillance, sequence, climate, and demographic data between 1 April 2010 and 31 March 2018 from continental China, to characterize detailed transmission patterns and explore the potential initiating region and drivers of the seasonal influenza epidemics in China. Results An annual cycle for influenza A(H1N1)pdm09 and B and a semi-annual cycle for influenza A(H3N2) were confirmed. Overall, the seasonal influenza A(H3N2) virus caused more infection in China and dominated the summer season in the south. The summer season epidemics in southern China were likely initiated in the “Lingnan” region, which includes the three most southern provinces of Hainan, Guangxi, and Guangdong. Additionally, the regions in the south play more important seeding roles in maintaining the circulation of seasonal influenza in China. Though intense human mobility plays a role in the province-level transmission of influenza epidemics on a temporal scale, climate factors drive the spread of influenza epidemics on both the spatial and temporal scales. Conclusion The surveillance of seasonal influenza in the south, especially the “Lingnan” region in the summer, should be strengthened. More broadly, both the socioeconomic and climate factors contribute to the transmission of seasonal influenza in China. The patterns and mechanisms revealed in this study shed light on the precise forecasting, prevention, and control of seasonal influenza in China and worldwide.

Autoimmune diseases are increasingly linked to aberrant gut microbiome and relevant metabolites. However, the association between vitiligo and the gut microbiome remains to be elucidated. Thus, we conducted a case-control study through 16S rRNA sequencing and serum untargeted-metabolomic profiling based on 30 vitiligo patients and 30 matched healthy controls. In vitiligo patients, the microbial composition was distinct from that of healthy controls according to the analysis on α- and β-diversity (P < 0.05), with a characteristic decreased Bacteroidetes: Firmicutes ratio. Meanwhile, the levels of 23 serum metabolites (including taurochenodeoxycholate and L-NG-monomethyl-arginine) in the vitiligo patients were different from those in the healthy individuals and showed significant correlations with some microbial markers. We found that Corynebacterium 1, Ruminococcus 2, Jeotgalibaca and Psychrobacter were correlated significantly with disease duration and serum IL-1β level in vitiligo patients. And Psychrobacter was identified as the most predictive features for vitiligo by machine learning analysis (“importance” = 0.0236). Finally, combining multi-omics data and joint prediction models with accuracies up to 0.929 were established with dominant contribution of Corynebacterium 1 and Psychrobacter. Our findings replenished the previously unknown relationship between gut dysbiosis and vitiligo circulating metabolome and enrolled the gut-skin axis into the understanding of vitiligo pathogenesis.

The activation of NLRP3 inflammasome-IL-1β pathway in keratinocytes contributes to the melanocyte death via autoimmunity-dependent manner in vitiligo. As a safe small-compound drug employed frequently in clinic, tranilast (TR) is newly reported to block the activation of NLRP3 inflammasome in macrophage. Nevertheless, whether keratinocyte-derived IL-1β damages melanocytes in an autoimmunity-independent way and whether TR could ameliorate the melanocyte damage via inhibiting the NLRP3-IL-1β pathway in keratinocyte still are not clear. In the present study, we initially found that TR could impede the secretion of IL-1β from keratinocytes by interfering the NLRP3 oligomerization. More importantly, we illustrated that TR could decrease the melanocyte apoptosis, improve the melanogenesis, and have the capacity to optimize the melanosome translocation by abolishing the keratinocyte-derived IL-1β. Additionally, TR could mitigate the secretion of inflammatory cytokines such as IL-6, IL-8, TNF-α, and IL-18 in keratinocytes under oxidative stress. In short, our data indicate that IL-1β plays detrimental roles in the melanocyte survival, melanogenesis, melanosome translocation and the secretion of inflammatory cytokines, and TR could be a promising therapeutic strategy in vitiligo by attenuating the keratinocyte-derived IL-1β under oxidative stress.

The composition and structure of cement-stabilized macadam (CSM) is an important factor affecting its performance. Aiming at the typical suspension dense structure and skeleton dense structure, the static pressure and vibration methods were used to prepare the CSM samples. The three-dimensional internal structure characteristics of CSM were analyzed and studied by industrial CT scanning technology. By using digital image and 3D reconstruction technology, the structural parameters such as the number of 3D voids, the gradation of voids, the distribution of voids along the height direction, and the coefficient of variation of the proportion of coarse aggregate area were obtained. The results show that more than 80% of the voids in CSM are less than 1 mm3, and the number of large voids of skeleton dense gradation is more than that of suspension dense gradation under the two compaction methods. The distribution of internal voids along the height of CSM specimens cannot be changed by the compaction mode, but the vibration method can reduce its void ratio. Under different compaction methods, the variation coefficient of the coarse aggregate area ratio of two kinds of CSM mixture generally has the same change trend, and the vibration method can make its inner structure more uniform.

Characterizing the spatial transmission pattern is critical for better surveillance and control of human influenza. Here, we propose a mutation network framework that utilizes network theory to study the transmission of human influenza H3N2. On the basis of the mutation network, the transmission analysis captured the circulation pattern from a global simulation of human influenza H3N2. Furthermore, this method was applied to explore, in detail, the transmission patterns within Europe, the United States, and China, revealing the regional spread of human influenza H3N2. The mutation network framework proposed here could facilitate the understanding, surveillance, and control of other infectious diseases.