A retrospective study on the impact of radiotherapy on the survival outcomes of small cell lung cancer patients based on the SEER database.

Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan-Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients' overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P < 0.001). Competitive risk analysis showed that cancer-specific mortality was significantly higher in the non-radiotherapy group than in the radiotherapy group (P < 0.001). Multivariate Cox analysis showed that the radiotherapy group (relative non-radiotherapy group) showed a significant positive effect on survival outcomes (OS: HR 0.658 95% CI [0.642, 0.675] P < 0.001; CSS: HR 0.662 95% CI [0.645, 0.679], P < 0.001). In addition, age, gender, race, primary tumor site, T stage, N stage, M stage, chemotherapy, and surgery were also considered as important predictors of SCLC outcome. The results of the subgroup analysis showed that the radiotherapy group showed a significant survival advantage regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery (P < 0.001). Radiotherapy may improve both OS and CSS in SCLC patients. Patients with SCLC may benefit from radiotherapy regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery.

Bioinformatic analysis and identification of macrophage polarization-related genes in intervertebral disc degeneration.

BACKGROUND: The relationship between macrophage polarization-related genes (MPRGs) and intervertebral disc degeneration (IDD) is unclear. The purpose of this study was to identify biomarkers associated with IDD. METHODS: Three transcriptome sequencing datasets, GSE124272, GSE70362 and GSE56081 were included in this study. Differential expressed genes (DEGs) were obtained by overlapping DEGs1 from the GSE124272 and DEGs2 from the GSE70362. The key module genes associated with the score of MPRGs were identified by weighted gene co-expression network analysis (WGCNA) in GSE12472. Differentially expressed (DE)-MPRGs were acquired by overlapping key module genes and DEGs. Candidate genes were obtained by SVM-RFE algorithm. Biomarkers were obtained by expression level analysis. In addition, immune analysis, enrichment analysis and construction of a ceRNA network were completed. The blood samples from 9 IDD patients (IDD group) and 9 healthy individuals (Control group) were used to verify the expression levels of these biomarkers through RT-qPCR. RESULTS: A sum of 39 DEGs were obtained by overlapping DEGs1 and DEGs2, and 1,633 key module genes were obtained by WGCNA. 9 DE-MPRGs were obtained by overlapping DEGs and key module genes, and ST6GALNAC2, SMIM3, and IFITM2 were identified as biomarkers. These biomarkers were enriched in KEGG_RIBOSOME pathway. Check-point, Cytolytic_activity, T_cell_co-stimulation, Neutrophils, Th2_cells and TIL differed between IDD and control groups. Some relationships such as SMIM3-hsa-miR-107-LINC02381 were identified in the network. Moreover, the functional analysis results of biomarkers showed that FITM2 and SMIM3 could predict IDD and nociceptive pain. The RT-qPCR showed that ST6GALNAC2 and IFITM2 were significantly expressed in IDD group in contrast to the control group. CONCLUSION: The macrophage polarization related biomarkers (ST6GALNAC2, SMIM3 and IFITM2) were associated with IDD, among which IFITM2 could be considered as a key gene for IDD. This may provide a new direction for the biological treatment and mechanism research into IDD.

Coordinated molecular and ecological adaptations underlie a highly successful parasitoid.

The success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid, Trichopria drosophilae, which parasitizes a broad range of Drosophila hosts, including the globally invasive species D. suzukii. We found that T. drosophilae had developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell-teratocytes-that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.

Enhanced Mineralization of Organic Pollutants through Atomic Hydrogen-Mediated Alternative Transformation Pathways.

Electrocatalytic hydrogen atom-hydroxyl radical (H*-·OH) redox system is a promising approach for contaminant removal and mineralization. However, its working mechanism, especially the effect of H*, remains unclear, hindering its practical application. Herein, we constructed an electrochemical reactor equipped with our self-made Pd-loaded Ti/TiO2 nanotube cathode and a commercial boron-doped diamond anode. After fulfilling the electrode characterization and free radical detection, we employed coumarin and 7-azido-4-methylcoumarin as probes to confirm the participation of H* in the transformation of organic compounds. A comprehensive study on the degradation kinetics, reaction, and mineralization mechanisms using benzoic acid (BA) and 4-chlorophenol (4-CP) as model compounds was further conducted. The rate constants and total organic carbon removal of BA and 4-CP in the redox system increased compared with those of the individual oxidation and reduction processes. Theoretical calculations demonstrate that H* opens up alternative pathways for BA and 4-CP ring cleavage, forming quinones as reactive intermediates. Furthermore, H* facilitates the mineralization of the typical intermediates, maleic acid and fumaric acid, through C=C bond addition and H-abstraction from the 1,1-diol structure. The presence of H* provides alternative pathways for pollutant transformation, consequently reducing the treatment duration.

Lead Identification of Novel Naphthyridine Derivatives as Potent SOS1 Inhibitors.

SOS1, a guanine nucleotide exchange factor (GEF), plays a critical role in catalyzing the conversion of KRAS from its GDP- to GTP-bound form, regardless of KRAS mutation status, and represents a promising new drug target to treat all KRAS-driven tumors. Herein, we employed a scaffold hopping strategy to design, synthesize, and optimize a series of novel binary ring derivatives as SOS1 inhibitors. Among them, compound 10f (HH0043) displayed potent activities in both biochemical and cellular assays and favorable pharmacokinetic profiles. Oral administration of HH0043 resulted in a significant tumor inhibitory effect in a subcutaneous KRAS G12C-mutated NCI-H358 (human lung cancer cell line) xenograft mouse model, and the tumor inhibitory effect of HH0043 was superior to that of BI-3406 at the same dose (total growth inhibition, TGI: 76% vs 49%). On the basis of these results, HH0043, with a novel 1,7-naphthyridine scaffold that is distinct from currently reported SOS1 inhibitors, is nominated as the lead compound for this discovery project.

Evaluation of the therapeutic effect of Sacha inchi oil in atopic dermatitis mice.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition characterized by a multifaceted pathogenesis, which encompasses immune system signaling dysregulation, compromised skin barrier function, and genetic influencers. Sacha inchi (Plukenetia volubilis L.) oil (SIO) has demonstrated potent anti-inflammatory and antioxidant properties, however, the mechanism underlying the beneficial effects of SIO on AD remains unclear. This study aims to investigate the anti-AD effect of SIO and its possible molecular mechanism in mice with AD. The results demonstrated that SIO significantly reduced the degree of skin lesions and scratching, and improved the skin thickness and mast cell infiltration in AD mice. Furthermore, SIO significantly reduced the levels of immunoglobulin E, histamine and thymic stromal lymphopoietin in serum of AD mice. Additionally, it inhibited the expression of tumor necrosis factor-γ, interferon-γ, interleukin-2, interleukin-4, interleukin 1ß and other inflammatory cytokines in the lesions skin of mice. The Western blotting analysis revealed that SIO exhibited an upregulatory effect on the protein expression of filaggrin and loricrin, while concurrently exerting inhibitory effects on the protein expression and phosphorylation levels of P38, ERK, NF-κB, and IκBα within their respective signaling pathways. Consequently, it can be inferred that SIO exerts a significant anti-atopic dermatitis effect by modulating the P38, ERK, NF-κB, and IκBα signaling pathways. This study contributes to expand the research and development potential of SIO, and provides novel insights and potential therapeutic strategies for AD treatment.

Role of the Yersinia pestis phospholipase D (Ymt) in the initial aggregation step of biofilm formation in the flea.

Transmission of Yersinia pestis by fleas depends on the formation of condensed bacterial aggregates embedded within a gel-like matrix that localizes to the proventricular valve in the flea foregut and interferes with normal blood feeding. This is essentially a bacterial biofilm phenomenon, which at its end stage requires the production of a Y. pestis exopolysaccharide that bridges the bacteria together in a cohesive, dense biofilm that completely blocks the proventriculus. However, bacterial aggregates are evident within an hour after a flea ingests Y. pestis, and the bacterial exopolysaccharide is not required for this process. In this study, we characterized the biochemical composition of the initial aggregates and demonstrated that the yersinia murine toxin (Ymt), a Y. pestis phospholipase D, greatly enhances rapid aggregation following infected mouse blood meals. The matrix of the bacterial aggregates is complex, containing large amounts of protein and lipid (particularly cholesterol) derived from the flea's blood meal. A similar incidence of proventricular aggregation occurred after fleas ingested whole blood or serum containing Y. pestis, and intact, viable bacteria were not required. The initial aggregation of Y. pestis in the flea gut is likely due to a spontaneous physical process termed depletion aggregation that occurs commonly in environments with high concentrations of polymers or other macromolecules and particles such as bacteria. The initial aggregation sets up subsequent binding aggregation mediated by the bacterially produced exopolysaccharide and mature biofilm that results in proventricular blockage and efficient flea-borne transmission. IMPORTANCE: Yersinia pestis, the bacterial agent of plague, is maintained in nature in mammal-flea-mammal transmission cycles. After a flea feeds on a mammal with septicemic plague, the bacteria rapidly coalesce in the flea's digestive tract to form dense aggregates enveloped in a viscous matrix that often localizes to the foregut. This represents the initial stage of biofilm development that potentiates transmission of Y. pestis when the flea later bites a new host. The rapid aggregation likely occurs via a depletion-aggregation mechanism, a non-canonical first step of bacterial biofilm development. We found that the biofilm matrix is largely composed of host blood proteins and lipids, particularly cholesterol, and that the enzymatic activity of a Y. pestis phospholipase D (Ymt) enhances the initial aggregation. Y. pestis transmitted by flea bite is likely associated with this host-derived matrix, which may initially shield the bacteria from recognition by the host's intradermal innate immune response.

Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas.

Endobronchial leiomyomas are rare benign neoplasms of the lungs that arise from the smooth muscle cells of the bronchi and bronchioles. While surgical resection is the mainstay of treatment for these tumors, bronchoscopic interventional therapies are also effective and can help preserve lung function in certain cases. A 40-year-old male patient presented with a persistent cough and sputum production for over 4 months. A chest computed tomography scan revealed nodular lesions in the lower lobe bronchus, later confirmed as an endobronchial leiomyoma. The patient refused surgical intervention and opted for minimally invasive bronchoscopic treatments, including electric snare resection, argon plasma coagulation, and balloon dilation, resulting in a successful outcome with no recurrence during follow-up. Clinicians should consider bronchoscopic interventions as a viable treatment option for endobronchial leiomyomas patients who are either ineligible for surgical resection or opt not to undergo surgery.

Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities.

White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low-grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity-related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota.

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1ß secretion.

Occurrence, fate, and risk assessment of antibiotics in conventional and advanced drinking water treatment systems: From source to tap.

The occurrence and removal of 38 antibiotics from nine classes in two drinking water treatment plants (WTPs) were monitored monthly over one year to evaluate the efficiency of typical treatment processes, track the source of antibiotics in tap water and assess their potential risks to ecosystem and human health. In both source waters, 18 antibiotics were detected at least once, with average total antibiotic concentrations of 538.5 ng/L in WTP1 and 569.3 ng/L in WTP2. The coagulation/flocculation and sedimentation, sand filtration and granular activated carbon processes demonstrated limited removal efficiencies. Chlorination, on the other hand, effectively eliminated antibiotics by 48.7 ± 11.9%. Interestingly, negative removal was observed along the distribution system, resulting in a significant antibiotic presence in tap water, with average concentrations of 131.5 ng/L in WTP1 and 362.8 ng/L in WTP2. Source tracking analysis indicates that most antibiotics in tap water may originate from distribution system. The presence of antibiotics in raw water and tap water posed risks to the aquatic ecosystem. Untreated or partially treated raw water could pose a medium risk to infants under six months. Water parameters, for example, temperature, total nitrogen and total organic carbon, can serve as indicators to estimate antibiotic occurrence and associated risks. Furthermore, machine learning models were developed that successfully predicted risk levels using water quality parameters. Our study provides valuable insights into the occurrence, removal and risk of antibiotics in urban WTPs, contributing to the broader understanding of antibiotic pollution in water treatment systems.

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae.

Fungal meroterpenoids are diverse structurally intriguing molecules with various biological properties. One large group within this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10'R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids.

REMIMAZOLAM IMPROVES THE MARKERS OF POSTRESUSCITATION CEREBRAL INJURY IN A SWINE MODEL OF CARDIAC ARREST.

ABSTRACT: Introduction: Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods: A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of CPR. Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Postresuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h after resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage, including tissue inflammation, oxidative stress, apoptosis, and necroptosis. Results: Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the sham group. However, remimazolam postconditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group. Conclusions: In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.

Genomic heterogeneity of multiple synchronous lung cancers in Chinese population.

INTRODUCTION: It is clinically challenging to infer the phylogenetic relationship between different tumor lesions of patients with multiple synchronous lung cancers (MSLC), whether these lesions are the result of independently evolved tumor or intrapulmonary metastases. METHODS: We used the Illumina X10 platform to sequence 128 stage I lung cancer samples collected from 64 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference. RESULTS: We detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including, EGFR, ERBB2, TP53, BRAF, and KRAS. Other putative driver mutations identified were enriched in RTK-RAS signaling, TP53 signaling, and cell cycle. Also, we found some interesting cases, two cases that carried EGFR L858R and T790M co-mutation in one tumor and another tumor with only EGFR 19del, and 1 case with two KRAS hotspots in the same tumor. Due to the short follow-up time and early stage, further investigation is needed to determine whether this unique mutation profile will affect their progression-free survival (PFS) and overall survival (OS). Regarding genetic evolution analysis among 64 tumor samples, 50 of them display distinct mutational profiles, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. On the other hand, six patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. CONCLUSION: In summary, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profiles in different tumor lesions, and we could distinguish MSLC from intrapulmonary metastases via clonality estimation.

A comprehensive analysis of immunotherapy in advanced endometrial cancer (Review).

The morbidity and mortality rates of endometrial cancer (EC) are increasing yearly. Early-stage EC can be effectively treated through surgery or surgery combined with radiotherapy and chemotherapy. Advanced and recurrent EC is treated with chemotherapy and comprehensive treatment; however, the prognosis for patients at this disease stage is poor. Consequently, novel and effective treatment strategies are urgently required for these patients. Breakthrough progress has been made with the use of immunosuppressants in the treatment of EC, which have been included in treatment guidelines. In the present review, the etiology and classification of EC was outlined and the relevant scientific basis for the application of immunosuppressants in advanced and recurrent EC was discussed. The relevant published and ongoing clinical trials are also summarized. As such, the present review aimed to provide a scientific summary of immunotherapy of EC.

AI-ChatGPT/GPT-4: An Booster for the Development of Physical Medicine and Rehabilitation in the New Era!

Artificial intelligence (AI) has been driving the continuous development of the Physical Medicine and Rehabilitation (PM&R) fields. The latest release of ChatGPT/GPT-4 has shown us that AI can potentially transform the healthcare industry. In this study, we propose various ways in which ChatGPT/GPT-4 can display its talents in the field of PM&R in future. ChatGPT/GPT-4 is an essential tool for Physiatrists in the new era.

Targeted amplicon sequencing facilitated a novel risk assessment framework for assessing the prevalence of broad spectrum bacterial and coronavirus diseases.

How to effectively leverage wastewater data to estimate the risk of various infectious diseases remains a great challenge. To address this issue, we conducted continuous wastewater surveillance in Dalian city during the summer-autumn seasons of 2022, targeting coronavirus and bacterial diseases. The surveillance included daily sampling at a wastewater treatment plant (WWTP) and weekly sampling in three sewersheds. Targeting the bacteria's 16S rRNA gene and the coronavirus's RNA-dependent RNA polymerase (RdRp) gene, we first employed RT-PCR and amplicon sequencing techniques to analyze the presence and phylogenetic relationship of detected coronavirus and bacterial pathogens. Next, qPCR was used to quantify the abundances of detected coronavirus and bacterial species. Based on the daily shedding dynamics of SARS-CoV-2, a novel model was developed to predict daily new cases. Based on the medium shedding density of 12 pathogens, two thresholds of sewage pathogen load (indicating 0.1 % and 1 % infection rates) were proposed. Our PanCoV RT-PCR detected coronavirus on 12th August and from 26th August to 12th September 2022. Targeted amplicon sequencing further identified human coronavirus OC43 (hCoV-OC43) on 12th August and the SARS-CoV-2 Omicron variant since 26th August in samples from WWTPs and sewersheds. Phylogenetic analysis revealed that hCoV-OC43 from this study belonged to genotype K and suggested a close relationship between the amplified coronavirus sequences from wastewater and clinical samples in a local COVID-19 outbreak on 26th August. Amplicon sequencing targeting the bacterial 16S rRNA gene also revealed the presence of several bacterial pathogens. Finally, we assessed the microbial risk of specific pathogens in sewersheds and identified a number of pathogens that reached high (>1 % prevalence) and medium risk levels (>0.1 % prevalence) at sewershed B. Our findings underline wastewater surveillance as a valuable early warning system for coronavirus and other waterborne bacterial diseases, complementing public health response measures.

Longitudinal wastewater surveillance of four key pathogens during an unprecedented large-scale COVID-19 outbreak in China facilitated a novel strategy for addressing public health priorities-A proof of concept study.

Wastewater-based epidemiology (WBE) is a promising tool for monitoring the spread of SARS-CoV-2 and other pathogens, providing a novel public health strategy to combat disease. In this study, we first analysed nationwide reports of infectious diseases and selected Salmonella, norovirus, and influenza A virus (IAV) as prioritized targets apart from SARS-CoV-2 for wastewater surveillance. Next, the decay rates of Salmonella, norovirus, and IAV in wastewater at various temperatures were established to obtain corrected pathogen concentrations in sewage. We then monitored the concentrations of these pathogens in wastewater treatment plant (WWTP) influents in three cities, establishing a prediction model to estimate the number of infected individuals based on the mass balance between total viral load in sewage and individual viral shedding. From October 2022 to March 2023, we conducted multipathogen wastewater surveillance (MPWS) in a WWTP serving one million people in Xi'an City, monitoring the concentration dynamics of SARS-CoV-2, Salmonella, norovirus, and IAV in sewage. The infection peaks of each pathogen were different, with Salmonella cases and sewage concentration declining from October to December 2022 and only occasionally detected thereafter. The SARS-CoV-2 concentration rapidly increased from December 5th, peaked on December 26th, and then quickly decreased until the end of the study. Norovirus and IAV were detected in wastewater from January to March 2023, peaking in February and March, respectively. We used the prediction models to estimate the rate of SARS-CoV-2 infection in Xi'an city, with nearly 90 % of the population infected in urban regions. There was no significant difference between the predicted and actual number of hospital admissions for IAV. We also accurately predicted the number of norovirus cases relative to the reported cases. Our findings highlight the importance of wastewater surveillance in addressing public health priorities, underscoring the need for a novel workflow that links the prediction results of populations with public health interventions and allocation of medical resources at the community level. This approach would prevent medical resource panic squeezes, reduce the severity and mortality of patients, and enhance overall public health outcomes.