RESUMEN

Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Asunto(s)

COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , China/epidemiología , Estudios Retrospectivos , Hospitalización/estadística & datos numéricos , Teorema de Bayes , Política de Salud , Pandemias

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We have developed a cryogen-free, low-temperature terahertz scanning tunneling microscope (THz-STM). This system utilizes a continuous-flow cryogen-free cooler to achieve low temperatures of ∼25 K. Meanwhile, an ultra-small ultra-high vacuum chamber results in the reduction of the distance from sample to viewport to only 4 cm. NA = 0.6 can be achieved while placing the entire optical component, including a large parabolic mirror, outside the vacuum chamber. Thus, the convenience of optical coupling is much improved without compromising the performance of STM. Based on this, we introduced THz pulses into the tunnel junction and constructed the THz-STM, achieving atomic-level spatial resolution in THz-driven current imaging and sub-picosecond (sub-ps) time resolution in autocorrelation signals during pump-probe measurements. Experimental data from various representative samples are presented to showcase the performance of the instrument, establishing it as an ideal platform for studying non-equilibrium dynamic processes at nanoscale.

RESUMEN

The endoplasmic reticulum (ER) is a unique organelle responsible for protein synthesis and processing, lipid synthesis in eukaryotic cells, and the replication of many animal viruses is closely related to ER. A considerable number of viral proteins are synthesised during viral infection, resulting in the accumulation of unfolded and misfolded proteins in ER, which in turn induces endoplasmic reticulum stress (ERS). ERS further drives three signalling pathways (PERK, IRE1, and ATF6) of the cellular unfolded protein response (UPR) to respond to the ERS. In numerous studies, ERS has been shown to mediate autophagy, a highly conserved cellular degradation mechanism to maintain cellular homeostasis in eukaryotic cells, through the UPR to restore ER homeostasis. ERS-mediated autophagy is closely linked to the occurrence and development of numerous viral diseases in animals. Host cells can inhibit viral replication by regulating ERS-mediated autophagy, restoring the ER's normal physiological process. Conversely, many viruses have evolved strategies to exploit ERS-mediated autophagy to achieve immune escape. These strategies include the regulation of PERK-eIF2α-Beclin1, PERK-eIF2α-ATF4-ATG12, IRE1α-JNK-Beclin1, and other signalling pathways, which provide favourable conditions for the replication of animal viruses in host cells. The ERS-mediated autophagy pathway has become a hot topic in animal virological research. This article reviews the most recent research regarding the regulatory functions of ERS-mediated autophagy pathways in animal viral infections, emphasising the underlying mechanisms in the context of different viral infections. Furthermore, it considers the future direction and challenges in the development of ERS-mediated autophagy targeting strategies for combating animal viral diseases, which will contribute to unveiling their pathogenic mechanism from a new perspective and provide a scientific reference for the discovery and development of new antiviral drugs and preventive strategies.

Asunto(s)

Autofagia , Estrés del Retículo Endoplásmico , Virosis , Autofagia/fisiología , Animales , Estrés del Retículo Endoplásmico/fisiología , Virosis/veterinaria , Virosis/virología , Transducción de Señal

RESUMEN

To explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated BP in children and adolescents. Both a nested case control and a cohort study were designed to explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated blood pressure (BP). All the included participants were from primary school. A total of 326 subjects (116:210) in nested case control were from an established cohort. And 270 participants without hypertension at baseline and followed in 2019 in cohort. FA and VB12 levels were lower in the elevated BP group than in the control group, and homocysteine level was higher than that in the control group. In the elevated BP group, overweight/obese children had lower FA than overweight/obese children in the normal BP group. FA was positively correlated with high-density lipoprotein (HDL) and Apo lipoprotein A (APOA), but negatively correlated with triglyceride (TG). FA was significantly correlated with elevated BP in children and adolescents (ß = -0.353, P = 0.032), after adjusting VB12, and homocysteine (HCY), and the interaction effect of FA*HCY was significant. Both systolic and diastolic BP levels were statistically lower in the FA high exposure group than in the FA low exposure group in the cohort study. This study found that FA and vitamin B12 deficiency in childhood was correlated with elevated BP levels, which may affect BP by regulating lipid levels, and confirmed the importance of maintaining high levels of FA and vitamin B12 in childhood either by diet or supplementation.

RESUMEN

Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.

Asunto(s)

Disfunción Eréctil , Hiperuricemia , Inflamasomas , Janus Quinasa 2 , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Janus Quinasa 2/metabolismo , Masculino , Inflamasomas/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Disfunción Eréctil/metabolismo , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

The ruby lattice is one of the tight-binding models which hosts a flat band in its electronic structure and has potential applications in future spintronics and quantum devices. However, the experimental realization of a ruby lattice in realistic materials remains elusive. Here, we have experimentally realized an atomic ruby lattice by fabricating monolayer CuCl1+x on a Au(111) substrate. Scanning tunneling microscopy/spectra (STM/STS) measurements combined with density-functional theory (DFT) calculations reveal that the Cu atoms are arranged in a ruby lattice in this monolayer. Moreover, a significant density of states (DOS) peak corresponding to the characteristic of a ruby system is observed, consistent with both the tight-binding model and first-principles calculations on the band structure. Our work provides a promising platform to explore the physics of the ruby model.

RESUMEN

RATIONALE: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. PATIENT CONCERNS: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. DIAGNOSIS: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. INTERVENTIONS: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. OUTCOMES: Currently, the patient demonstrates a stable disease by clinical evaluation. LESSONS: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Asunto(s)

Adenolinfoma , Linfoma de Células del Manto , Neoplasias de la Parótida , Humanos , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/complicaciones , Linfoma de Células del Manto/diagnóstico , Femenino , Anciano , Adenolinfoma/patología , Adenolinfoma/complicaciones , Adenolinfoma/cirugía , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/complicaciones , Glándula Parótida/patología , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/cirugía

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The Weyl semimetals represent a distinct category of topological materials wherein the low-energy excitations appear as the long-sought Weyl Fermions. Exotic transport and optical properties are expected because of the chiral anomaly and linear energy-momentum dispersion. While three-dimensional Weyl semimetals have been successfully realized, the quest for their two-dimensional (2D) counterparts is ongoing. Here, we report the realization of 2D Weyl Fermions in monolayer PtTe1.75, which has strong spin-orbit coupling and lacks inversion symmetry, by combined angle-resolved photoemission spectroscopy, scanning tunneling microscopy, second harmonic generation, X-ray photoelectron spectroscopy measurements, and first-principles calculations. The giant Rashba splitting and band inversion lead to the emergence of three pairs of critical Weyl cones. Moreover, monolayer PtTe1.75 exhibits excellent chemical stability in ambient conditions, which is critical for future device applications. The discovery of 2D Weyl Fermions in monolayer PtTe1.75 opens up new possibilities for designing and fabricating novel spintronic devices.

RESUMEN

Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.

Asunto(s)

Apoptosis , Ciclooctanos , Lignanos , Lipopolisacáridos , Compuestos Policíclicos , Células de Sertoli , Animales , Masculino , Ciclooctanos/farmacología , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/uso terapéutico , Lignanos/farmacología , Lignanos/uso terapéutico , Apoptosis/efectos de los fármacos , Ratones , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Receptores Androgénicos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Simulación del Acoplamiento Molecular , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , FN-kappa B/metabolismo

RESUMEN

Background: The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset. Methods: We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group. Results: From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (ß -0.05, 95% CI [-0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50-1.00; P = 0.0508). Conclusion: Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.

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Fertilization significantly influences soil quality and its sustainable use in urban garden maintenance. The widespread application of inorganic fertilizers has raised ecological concerns due to their potential environmental impacts. Organic fertilizers, while beneficial, often have slow effects and are costly. Biofertilizers, with their eco-friendly nature and low carbon footprint, are gaining attention for their multifaceted role in supporting plant growth. Despite the focus on fruit trees, vegetables, and medicinal plants, ornamental plants have been understudied. This study aims to evaluate the efficacy of a novel microbial fertilizer, 'natural soil biotin', on Rhododendron plants, specifically the Azalea hybrid 'Carnation'. The study employed a comparative approach to assess the impact of different fertilization strategies on soil properties, microbial diversity, enzyme activity, plant morphology, and physiological parameters. The application of 'natural soil biotin' was compared with the use of inorganic and organic fertilizers. The combined application of 'natural soil biotin' was found to effectively enhance soil properties and mitigate the impact of other fertilizers on soil pH. It also improved the relative abundance of beneficial microbial groups such as Proteobacteria, Ascomycota, and Basidiomycota. Furthermore, the mixed application significantly increased the activities of urease and sucrase in Rhododendron plants, which promoted their growth, development, and stress resistance. The results indicate that the mixed application of 'natural soil biotin' with inorganic and organic fertilizers not only improved the soil quality but also enhanced the efficiency of fertilizer utilization. This approach led to increased economic and environmental benefits in Rhododendron cultivation. The findings contribute to the foundation for soil improvement and ecological restoration, suggesting that 'natural soil biotin' could be a promising alternative or supplement to traditional fertilization methods in sustainable landscape architecture.

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Electricity-driven oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) is a highly attractive strategy for biomass transformation. However, achieving industrial-grade current densities remains a great challenge. Herein, by modulating the water content in a solvothermal system, Ni3S2/NF with stabilized and shorter Ni-S bonds as well as a tunable coordination environment of Ni sites was fabricated. The prepared Ni3S2/NF was highly efficient for electrocatalytic oxidation of HMF to produce FDCA, and the FDCA yield and Faraday efficiency could reach 98.8% and 97.6% at the HMF complete conversion. More importantly, an industrial-grade current density of 1000 mA cm-2 could be achieved at a potential of only 1.45 V vs. RHE for HMFOR and the current density could exceed 500 mA cm-2 with other bio-based compounds as the reactants. The excellent performance of Ni3S2/NF originated from the shorter Ni-S bonds and its better electrochemical properties, which significantly promoted the dehydrogenation step of oxidizing HMF. Besides, the gram-scale FDCA production could be realized on Ni3S2/NF in a MEA reactor. This work provides a robust electrocatalyst with high potential for practical applications for the electrocatalytic oxidation of biomass-derived compounds.

RESUMEN

Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.

RESUMEN

Pain in photodynamic therapy (PDT), resulting from the stimulation of reactive oxygen species (ROS) and local acute inflammation, is a primary side effect of PDT that often leads to treatment interruption or termination, significantly compromising the efficacy of PDT and posing an enduring challenge for clinical practice. Herein, a ROS-responsive nanomicelle, poly(ethylene glycol)-b-poly(propylene sulphide) (PEG-PPS) encapsulated Ce6 and Lidocaine (LC), (ESCL) was used to address these problems. The tumor preferentially accumulated micelles could realize enhanced PDT effect, as well as in situ quickly release LC due to its ROS generation ability after light irradiation, which owes to the ROS-responsive property of PSS. In addition, PSS can suppress inflammatory pain which is one of the mechanisms of PDT induced pain. High LC-loaded efficiency (94.56 %) owing to the presence of the thioether bond of the PPS made an additional pain relief by inhibiting excessive inflammation besides blocking voltage-gated sodium channels (VGSC). Moreover, the anti-angiogenic effect of LC offers further therapeutic effects of PDT. The in vitro and in vivo anti-tumor results revealed significant PDT efficacy. The signals of the sciatic nerve in mice were measured by electrophysiological study to evaluate the pain relief, results showed that the relative integral area of neural signals in ESCL-treated mice decreased by 49.90 % compared to the micelles without loaded LC. Therefore, our study not only develops a very simple but effective tumor treatment PDT and in situ pain relief strategy during PDT, but also provides a quantitative pain evaluation method.

Asunto(s)

Lidocaína , Micelas , Fotoquimioterapia , Especies Reactivas de Oxígeno , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones , Lidocaína/farmacología , Lidocaína/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Polietilenglicoles/química , Polietilenglicoles/farmacología , Dolor/tratamiento farmacológico , Humanos , Porfirinas/química , Porfirinas/farmacología , Sulfuros/química , Sulfuros/farmacología , Ratones Endogámicos BALB C , Tamaño de la Partícula , Nanopartículas/química , Clorofilidas

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infection may be associated with colorectal polyps/adenomas, but the current evidence remains controversial. METHODS: We retrospectively screened the medical records of 655 participants who underwent both colonoscopy and H. pylori test from June 15, 2020 to April 30, 2023. The number, size, location, and pathological type of colorectal polyps/adenomas were compared between H. pylori positive and negative groups. Adjusting for age, gender, smoking, drinking, hypertension, diabetes, fatty liver, body mass index, and inflammatory and metabolic indicators, multivariate logistic regression analyses were performed to evaluate the association of H. pylori infection with the number, size, location, and pathological type of colorectal polyps/adenomas, where no polyp/adenoma was used as reference. RESULTS: Overall, 508 participants were included, of whom 154 and 354 were divided into H. pylori positive and negative groups, respectively. H. pylori positive group had significantly higher colorectal polyps/adenomas (74.7 % vs. 65.8 %, P=0.048), low-grade adenomas (55.7 % vs. 47.6 %, P=0.026), advanced adenomas (22.6 % vs. 13.3 %, P=0.008), and colorectal polyps/adenomas with sizes of ≥6 mm (61.7 % vs. 48.5 %, P=0.002) and ≥10 mm (25.2 % vs. 14.6 %, P=0.004) than H. pylori negative group. In multivariate logistic regression analyses, H. pylori infection was independently associated with low-grade adenomas (OR=2.677, 95 %CI=1.283-5.587, P=0.009), advanced adenomas (OR=3.017, 95 %CI=1.007-9.036, P=0.049), right-side colon polyps/adenomas (OR=5.553, 95 %CI=1.679-18.360, P=0.005), and colorectal polyps/adenomas with sizes of ≥10 mm (OR=4.436, 95 %CI=1.478-13.310, P=0.008), but not number of colorectal polyps/adenomas. CONCLUSION: H. pylori infection is associated with increased risk of colorectal polyps/adenomas, especially low-grade adenomas, advanced adenomas, right-side colon polyps/adenomas, and large colorectal polyps/adenomas.

Asunto(s)

Adenoma , Pólipos del Colon , Colonoscopía , Neoplasias Colorrectales , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Femenino , Masculino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Persona de Mediana Edad , Estudios Transversales , Estudios Retrospectivos , Helicobacter pylori/aislamiento & purificación , Adenoma/epidemiología , Adenoma/microbiología , Adenoma/patología , Pólipos del Colon/epidemiología , Pólipos del Colon/microbiología , Pólipos del Colon/patología , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/etiología , Adulto , Anciano , Factores de Riesgo

RESUMEN

INTRODUCTION: Creating induced pluripotent stem cells (iPSCs) from somatic cells of patients with genetic diseases offers a pathway to generate disease-specific iPSCs carrying genetic markers. Differentiating these iPSCs into renal tubular cells can aid in understanding the pathophysiology of rare inherited renal tubular diseases through cellular experiments. MATERIALS AND METHODS: Two Japanese patients with Pseudohypoparathyroidism (PHP), a 49-year-old woman and a 71-year-old man, were studied. iPSC-derived tubular cells were established from their peripheral blood mononuclear cells (PBMCs). We examined changes in intracellular and extracellular cyclic adenosine monophosphate (cAMP) levels in these cells in response to parathyroid hormone (PTH) stimulation. RESULTS: Renal tubular cells, differentiated from iPSCs of a healthy control (648A1), showed a PTH-dependent increase in both intracellular and extracellular cAMP levels. However, the renal tubular cells derived from the PHP patients' iPSCs showed inconsistent changes in cAMP levels upon PTH exposure. CONCLUSION: We successfully created disease-specific iPSCs from PHP patients' PBMCs, differentiated them into tubular cells, and replicated the distinctive response of the disease to PTH in vitro. This approach could enhance our understanding of the pathophysiology of inherited renal tubular diseases and contribute to developing effective treatments.

Asunto(s)

Diferenciación Celular , AMP Cíclico , Células Madre Pluripotentes Inducidas , Túbulos Renales , Leucocitos Mononucleares , Hormona Paratiroidea , Seudohipoparatiroidismo , Humanos , Hormona Paratiroidea/farmacología , Hormona Paratiroidea/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Seudohipoparatiroidismo/genética , Seudohipoparatiroidismo/metabolismo , Femenino , Diferenciación Celular/efectos de los fármacos , Masculino , AMP Cíclico/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/patología , Persona de Mediana Edad , Anciano , Leucocitos Mononucleares/metabolismo , Células Cultivadas

RESUMEN

A novel deoxygenative alkynylation of amides promoted by a synergistic action of a divalent rare-earth element and a transition metal has been developed. In this method, α-alkynyl substituted amines are synthesized from unactivated amides and alkynes in a single transformation. Broad substrate scope and excellent selectivity for CO cleavage has been demonstrated. This approach represents a general method for the construction of versatile α-alkynyl substituted amines from unactivated amide bonds.