Nonlocal photonic quantum gates over 7.0 km.

Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

Imperatorin ameliorates ferroptotic cell death, inflammation, and renal fibrosis in a unilateral ureteral obstruction mouse model.

BACKGROUND: Imperatorin is a naturally occurring furocoumarin derivative found in traditional Chinese medicine Angelica dahurica for its anticancer, antihypertensive, and antidiabetic properties. Chronic kidney disease (CKD) is a global health issue, characterized by a high prevalence, significant morbidity and mortality, and a range of related complications. OBJECTIVE: This study aims to investigate the protective effects of imperatorin treatment and the specific underlying mechanisms in progressive CKD. METHODS: Imperatorin was orally administrated for 14 consecutive days to mice with unilateral ureteral obstruction (UUO) to investigate the renal pathological alternations, pro-inflammatory mediators, antioxidant response, and ferroptotic death signaling. Imperatorin was also tested in the erastin-induced injury of renal proximal tubular cells (NRK-52E). Cell viability, ferroptosis protein markers, erastin-induced oxidative stress, and lipid peroxidation were assessed. RESULTS: In vivo, imperatorin treatment alleviated kidney histology alternations and attenuated the protein expression of fibrotic markers. Furthermore, imperatorin administration reduced inflammatory cell infiltration, and alleviated the oxidative stress burden by downregulating protein markers such as catalase, superoxide dismutase 2 (SOD-2), NADPH oxidase 4 (NOX-4), and thioredoxin reductase 1 (Trxr-1). It also mitigated ferroptosis markers such as glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11/cystine transporter (SLC7A11/xCT), and transferrin receptor 1 (TFR-1), and attenuated renal cell apoptosis. In vitro, imperatorin treatment effectively decreased erastin-induced feroptotic cell death, restored the antioxidant enzyme levels, and mitigated lipid peroxidation as well as the expression of ferroptosis-related markers (XCT, GPX4, and p-p53) in a dose-dependent manner. CONCLUSION: Our finding demonstrated for the first time, that imperatorin treatment holds therapeutic potential in a UUO mouse model of CKD and inhibits the erastin-induced oxidative stress, ferroptosis, and subsequent lipid peroxidation in vitro. This highlights the potential of imperatorin as a future therapeutic target for ferroptosis to improve the progression of CKD.

Facile quantitative diagnostic testing for neutralizing antibodies against Chikungunya virus.

BACKGROUND: Viral neutralization (NT) assays can be used to determine the immune status of patients or assess the potency of candidate vaccines or therapeutic monoclonal antibodies (mAbs). Focus reduction neutralization test (FRNT) is a conventional neutralization test (cVNT) with superior specificity for measurement of neutralizing antibodies against a specific virus. Unfortunately, the application of FRNT to the chikungunya virus (CHIKV) involves a highly pathogenic bio-agent requiring biosafety level 3 (BSL3) facilities, which inevitably imposes high costs and limits accessibility. In this study, we evaluated a safe surrogate virus neutralization test (sVNT) that uses novel CHIKV replicon particles (VRPs) expressing eGFP and luciferase (Luc) to enable the rapid detection and quantification of neutralizing activity in clinical human serum samples. METHODS: This unmatched case-control validation study used serum samples from laboratory-confirmed cases of CHIKV (n = 19), dengue virus (DENV; n = 9), Japanese encephalitis virus (JEV; n = 5), and normal individuals (n = 20). We evaluated the effectiveness of sVNT, based on mosquito cell-derived CHIK VRPs (mos-CHIK VRPs), in detecting (eGFP) and quantifying (Luc) neutralizing activity, considering specificity, sensitivity, and reproducibility. We conducted correlation analysis between the proposed rapid method (20 h) versus FRNT assay (72 h). We also investigated the correlation between sVNT and FRNT in NT titrations in terms of Pearson's correlation coefficient (r) and sigmoidal curve fitting. RESULTS: In NT screening assays, sVNT-eGFP screening achieved sensitivity and specificity of 100%. In quantitative neutralization assays, we observed a Pearson's correlation coefficient of 0.83 for NT50 values between sVNT-Luc and FRNT. CONCLUSIONS: Facile VRP-based sVNT within 24 h proved highly reliable in the identification and quantification of neutralizing activity against CHIKV in clinical serum samples.

The neural circuit of Superior colliculus to ventral tegmental area modulates visual cue associated with rewarding behavior in optical intracranial Self-Stimulation in mice.

Visual system is the most important system of animal to cognize the information in outside world, and reward-related visual cues are the key factors in the consolidation and retrieval of reward memory. However, the neural circuit mechanism is still unclear. Superior Colliculus (SC) receive direct input from the retina and belong to the earliest stages of visual processing. Recent studies identified a specific pathway from SC to ventral tegmental area (VTA) that underlie specific innate behaviors, eg. flight or freezing, approach behaviors and so on. In present research, we investigated that inhibition of SC to VTA circuit with chemogenetics suppressed light cue-associated reward-seeking behaviors, while activation of the SC-VTA circuit with chemogenetic technology triggered the reward-seeking behaviors in optical intracranial self-stimulation for VTA DA neurons (oICSS) in mice. These findings suggest that neural circuit of SC-VTA mediates the retrieval of reward memory associated with visual cues, which will provide a new field for revealing the neural mechanism of pathological memory such as addiction.

Sinonasal teratocarcinosarcoma involving the nasal cavity, unilateral paranasal sinuses, and intracranial invasion: A case report.

BACKGROUND: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly invasive neoplasm originating from the nasal cavity and sinuses. Typically, it exhibits an invasive behavior towards adjacent structures; however, in exceptional instances, it may infiltrate the intracranial compartment. Due to the tumor's rarity and lack of distinctive features on computed tomography (CT) and magnetic resonance imaging (MRI) images, SNTCS is often misdiagnosed. CASE SUMMARY: In this study, we present a case of SNTCS in a 56-year-old patient who exhibited unexplained cognitive impairment before admission. CT and MRI scans revealed the presence of a mass in the right nasal cavity, with lesions extending to the right ethmoid sinus and right frontal region. Subsequently, the patient underwent pathological examination for confirmation and received surgical intervention to excise the tumor. The future advancement in our understanding of this disease will significantly contribute to the precise diagnosis and treatment of SNTCS. CONCLUSION: SNTCS is an exceptionally rare malignant tumor that originates from the nasal cavity and paranasal sinuses, presenting a diagnostic challenge due to its non-specific imaging findings. MRI accurately delineates the location, morphological characteristics, size, internal structure, extent of surrounding involvement, and metabolic information of the lesion. These aspects play a pivotal role in the precise localization and qualitative assessment of SNTCS. Nevertheless, a definitive diagnosis still requires a pathological biopsy.

Haemodynamic study of left nonthrombotic iliac vein lesions: a preliminary report.

Nonthrombotic iliac vein lesions (NIVLs) are significant causes of chronic venous insufficiency (CVI) in the left lower limb and symptom recurrence following left lower limb varicose vein treatment. The goal of this study was to explore the haemodynamic and morphological characteristics of iliac veins in patients with NIVLs. Pressure at the caudal end of the stenotic left common iliac vein (LCIV) segment, local blood flow velocity, and time-averaged wall shear stress in the stenotic segment exhibited positive correlations with the clinical CVI classification (R = 0.92, p < 0.001; R = 0.94, p < 0.001; R = 0.87, p < 0.001), while the relative retention time showed a negative correlation (R = -0.94, p < 0.001). The pressure difference (∆P) between the two ends of the stenotic segment and the velocity difference (∆V) between the stenotic segment and the caudal end were positively correlated with the clinical classification (R = 0.92, p < 0.001; R = 0.9, p < 0.001). The cross-sectional area stenosis rate and length of the stenotic LCIV segment were positively correlated with the clinical classification (R = 0.93, p < 0.001; R = 0.63, p < 0.001). The results suggest that haemodynamic assessment of the iliac vein could effectively portray blood flow disturbances in stenotic segments of the LCIV, potentially reflecting the degree of iliac vein stenosis. Haemodynamic indicators are correlated with the severity of clinical CVI symptoms.

Loop-Mediated Isothermal Amplification for Detecting Gly-4891-Glu and Ile-4734 Multiple Mutations of Ryanodine Receptor in the Fall Armyworm, Spodoptera frugiperda.

The key mutations, such as the Gly-4891-Glu substitution and the Ile-4734 multiple substitutions within the ryanodine receptors (RyR), are linked to diamide resistance in fall armyworm (FAW), Spodoptera frugiperda. In this study, we found that FAW remained sensitive to cyantraniliprole and chlorantraniliprole, while its sensitivity to flubendiamide was reduced. Moreover, a low level of heterozygous mutation at I4743 was observed. To facilitate the detection procedure of these mutations, a simple and efficient loop-mediated isothermal amplification (LAMP) protocol was developed for operation. The reaction for detecting the G4891E and I4743 single or multiple mutations was carried out at 68 °C for 85 min and 68 °C for 85 min or 68 °C for 65 min, respectively. These LAMP reactions can be easily observed via visualization of the color change from pink to yellow. This assay provides a simple, convenient, and effective means of detecting mutations in the RyR of FAW for pest management purposes.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Psychological factors associated with exercise self-efficacy in the recipients of an implantable cardioverter defibrillator.

BACKGROUND: Insufficient exercise affects the health of patients who have implantable cardioverter defibrillators (ICD). The purpose of this study was to investigate the correlations between exercise self-efficacy (ESE) and its associated psychological factors in ICD recipients. METHODS: This cross-sectional study included individuals who had undergone ICD implantation at the cardiology department of a medical centre in Taiwan. A face-to-face survey was conducted. The survey questionnaire included questions regarding the participants' demographics, perceived health (PH), ICD shock-related anxiety (ICD-SRA), self-care self-efficacy (SSE), perceived exercise benefit (PE-benefit), perceived exercise barrier (PE-barrier), and ESE. Data were analysed using SPSS 20.0 Software. Stepwise multiple regression analyses were also performed to evaluate the predictive effects of the aforementioned factors on ESE. RESULTS: A total of 52 ICD recipients were enrolled. ESE was negatively correlated with ICD-SRA (r = -0.511; p < 0.01) and PE-barrier (r = -0.563; p < 0.01), but positively correlated with SSE (r = 0.339; p < 0.05) and PE-benefit (r = 0.464; p < 0.01). The stepwise multiple regression analysis revealed that PE-barrier, PE-benefit, and ICD-SRA effectively predicted ESE in the participants. CONCLUSIONS: ESE may be improved by overcoming PE-barrier, ICD-SRA and enhancing PE-benefit. Consequently, improving ESE may enhance the health benefits of exercise.

Updated Gene Prediction of the Cucumber (9930) Genome through Manual Annotation.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of the predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (V3.1) contains an increased number (24,145) of predicted genes compared to the previous version (24,317 genes), with a higher BUSCO value of 96.9%. A total of 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjusted genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserved their original designations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using the newly obtained transcriptome data with the revised gene prediction model. This improved annotation of the cucumber genome will provide essential and accurate resources for studies in cucumber.

Desmethylclomipramine triggers mitochondrial damage and death in TGF-ß-induced mesenchymal type of A549 cells.

Lung cancer is the leading cause of cancer deaths, where the metastasis often causes chemodrug resistance and leads to recurrence after treatment. Desmethylclomipramine (DCMI), a bioactive metabolite of clomipramine, shows the therapeutic efficacy with antidepressive agency as well as potential cytostatic effects on lung cancer cells. Here, we demonstrated that DCMI effectively caused transforming growth factor (TGF)-ß1-mediated mesenchymal type of A549 cells to undergo mitochondrial death via myeloid cell leukemia-1 (Mcl-1) suppression and activation of truncated Bid (tBid). TGF-ß1 induced epithelial mesenchymal transition in A549 cells with the increase of fibronectin and decrease of E-cadherin, the activation of Akt/glycogen synthase kinase-3ß (GSK-ß)/Mcl-1 axis, and the hypo-responsiveness to cisplatin. DCMI initiated a dose-dependent cytotoxicity on TGF-ß1-mediated mesenchymal type of A549 cells through inactivating Akt/GSK-ß/Mcl-1 axis, in which mitochondria instability and caspase-9/3 activation also occurred concurrently. Pharmacological inhibition of caspase-8 and cathepsin B partly reversed tBid expression and mitochondrial damage to further attenuate DCMI-mediated cytotoxicity. Additionally, DCMI presented partial therapeutic effects in treating mesenchymal type of A549 tumor bearing nude mice through an acceleration of cancer cell death. Taken together, DCMI exerts antitumor effects via initiating the mechanisms of Akt/GSK-ß/Mcl-1 inactivation and cathepsin B/caspase-8-regulated mitochondrial death, which suggests its potential role in mesenchymal type of cancer cell therapy.

Prefrontal activity and heart rate variability during cognitive tasks may show different changes in young and older adults with and without mild cognitive impairment.

Background: Age-related decline in cognitive function is often linked to changed prefrontal cortex (PFC) activity and heart rate variability (HRV). Mild cognitive impairment (MCI), a transitional stage between normal aging and dementia, might have further degeneration beyond aging. This study aimed to investigate the differences between young and older adults with or without MCI in cognitive functions, task-induced PFC activation and HRV changes. Methods: Thirty-one healthy young adults (YA), 44 older adults (OA), and 28 older adults with MCI (OA-MCI) were enrolled and compared in this cross-sectional study. Each participant received a one-time assessment including cognitive and executive functions, as well as the simultaneous recording of PFC activity and HRV during a cognitive task paradigm. Results: We observed age-related decrease in global cognitive functions, executive functions, HRV, and increase in PFC activity. The MCI further deteriorated the global cognitive and executive performances, but not the HRV or the prefrontal activation. Conclusion: Older people showed lower performances in general cognitive function and executive function, compensatory increase of PFC activity, and reduced HRV. Older people with MCI had further deterioration in cognitive performance, but not in PFC activation and HRV.

Transcriptomic Insights and the Development of Microsatellite Markers to Assess Genetic Diversity in the Broodstock Management of Litopenaeus stylirostris.

The Pacific blue shrimp (Litopenaeus stylirostris) is a premium product in the international seafood market. However, intensified farming has increased disease incidence and reduced genetic diversity. In this study, we developed a transcriptome database for L. stylirostris and mined microsatellite markers to analyze their genetic diversity. Using the Illumina HiSeq 4000 platform, we identified 53,263 unigenes from muscle, hepatopancreas, the intestine, and lymphoid tissues. Microsatellite analysis identified 36,415 markers from 18,657 unigenes, predominantly dinucleotide repeats. Functional annotation highlighted key disease resistance pathways and enriched categories. The screening and PCR testing of 42 transcriptome-based and 58 literature-based markers identified 40 with successful amplification. The genotyping of 200 broodstock samples revealed that Na, Ho, He, PIC, and FIS values were 3, 0.54 ± 0.05, 0.43 ± 0.09, 0.41 ± 0.22, and 0.17 ± 0.27, respectively, indicating moderate genetic variability and significant inbreeding. Four universal microsatellite markers (CL1472.Contig13, CL517.Contig2, Unigene5692, and Unigene7147) were identified for precise diversity analysis in Pacific blue, Pacific white (Litopenaeus vannamei), and black tiger shrimps (Penaeus monodon). The transcriptome database supports the development of markers and functional gene analysis for selective breeding programs. Our findings underscore the need for an appropriate genetic management system to mitigate inbreeding depression, reduce disease susceptibility, and preserve genetic diversity in farmed shrimp populations.

MicroRNA-146a Signature in Psoriasis: A Systematic Review and Meta-Analysis.

BACKGROUND: Psoriasis is a chronic, inflammatory, T-cell-mediated disease with a multifactorial pathogenesis. MicroRNA (miRNA) alteration in psoriasis has been identified within the last few years. In particular, miR-146a levels were altered. However, previous studies have equivocal or even contradictory findings. OBJECTIVE: The current study aimed to perform a systematic review and meta-analysis to evaluate the miRNA expression profile in different tissues in patients with psoriasis. Further, the correlation between miR-146a levels and psoriasis severity as well as the specific expression patterns of the miR-146a profile in patients with psoriasis after treatment were evaluated. METHODS: To retrieve studies investigating the correlation between miRNA and psoriasis, a comprehensive search of databases including PubMed, Cochrane Library, and Embase was performed from inception to 30 June 2023. Relevant journals and references of the included studies were also reviewed. A meta-analysis was conducted using the comprehensive meta-analysis version 3. RESULTS: The correlation between the miR-146a expression levels and psoriasis susceptibility in 14 studies was assessed. Results showed that the miR-146a expression level was upregulated in psoriasis samples [P = 0.001, standardized mean difference (SMD) = 1.489, 95% confidence interval (CI) = 0.618-2.360]. In a subgroup analysis based on sample type, the correlation between the peripheral blood mononuclear cell, blood, and tissue miR-146a expression level and psoriasis was significant (SMD = 1.293, 95% CI 0.310-2.276, P = 0.01; SMD = 2.526, 95% CI 1.710-3.342, P = 0.000; SMD = 3.153, 95% CI 1.432-4.874, P = 0.00, respectively). A positive correlation was observed between the miR-146a expression levels and Psoriasis Area and Severity Index (PASI) score. However, the result was not statistically significant (correlation coefficient = 0.29, 95% CI - 0.038 to 0.575, P = 0.081). Further, the miR-146a levels decreased after treatment (SMD = - 1.592, 95% CI - 2.067 to - 1.117, P = 0.000, I2 = 74.104). CONCLUSIONS: The miR-146a expression level is positively correlated with and can contribute to the pathobiology of psoriasis.

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.

Association between colchicine use and the risk of dementia among patients with gout: A nationwide retrospective cohort study.

BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.

Determinants of Parental Intention to Vaccinate Young Adolescent Girls against the Human Papillomavirus in Taiwan: An Online Survey Study.

Since 2018, Taiwan has included the human papillomavirus (HPV) vaccination into its national immunization program for junior high school girls. However, the reports of side effects following vaccination have increased parental concerns. This study investigated parental intentions regarding the HPV vaccination for their daughters and related factors in Taiwan. A total of 213 parents of girls aged between 12 and 15 years participated in an online survey. The survey collected data on various factors, including the parental intention to vaccinate their daughters against HPV; the motivation behind the vaccinations, as measured using the Motors of Human Papillomavirus Vaccination Acceptance Scale; an understanding of the reasons behind the government's promotion of HPV vaccinations; concerns regarding the side effects of vaccinations for their daughters; an awareness of the reported side effects of HPV vaccines experienced by some individuals; the exposure to information on HPV vaccines from social media; and mental health status, measured using the Brief Symptom Rating Scale. The associations between these variables and the parental intention to vaccinate their daughters against HPV were examined using a multivariable linear regression analysis model. The findings revealed a moderate to high level of intention among participants to vaccinate their daughters against HPV. Parents who perceived a greater value in HPV vaccination for their daughters' health (B = 0.524, standard error [se] = 0.039, p < 0.001) and had greater autonomy in decision-making regarding vaccination (B = 0.086, se = 0.038, p = 0.026) exhibited a higher intention to vaccinate their daughters against HPV. Conversely, parents who expressed greater concern regarding the side effects of HPV vaccines for their daughters had a lower intention to vaccinate (B = -0.762, se = 0.203, p < 0.001). Based on these findings, this study recommends integrating these factors into the design of intervention programs aimed at enhancing parental intentions to vaccinate their daughters against HPV.