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1.
J Colloid Interface Sci ; 674: 1019-1024, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38968874

RESUMO

In response to the energy crisis caused by the exhaustion of fossil energy sources, as well as to combat global warming and achieve carbon neutrality, a sandwiched-structure fabric-based moisture-enabled electricity generator (SMEG) has been developed. Cotton fabric coated with MWCNT and PEDOT: PSS solution is used as the upper and bottom electrodes, while the acid-treated cotton fabric with coating PVA and HCl hydrogel electrolyte serves as the middle layer. A single SMEG can generate a maximum open-circuit voltage (Voc) of 0.44 V and a maximum short-circuit current (Isc) of 30 µA. When a drop of LiCl is dripped on one side of SMEGs, the maximum Voc and Isc increases to 0.57 V and 66 µA, respectively. The decline in output performance slows down when LiCl is applied. The Voc increases almost linearly in series and reaches 3.55 V when six SMEGs are connected, while the Isc increases linearly in parallel and reaches 204 µA when six SMEGs are connected. The maximum power density of a single SMEG yields 0.29 µW/cm2 with an external resistance of 1 kΩ. The series connection of six SMEGs successfully lit an LED and a calculator under ambient humidity conditions, demonstrating their potential application in small electronics.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 444-448, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38953269

RESUMO

The incidence of urinary calculi in children has been increasing annually,and most of the cases are upper urinary tract stones.At present,surgery is the main way to treat upper urinary tract stones in children.With the gradual development of minimally invasive techniques in surgery,percutaneous nephrolithotomy,retrograde intrarenal surgery,and extracorporeal shock wave lithotripsy have become the main methods for treating upper urinary tract stones in children.We reviewed the current progress in surgical treatment of upper urinary tract stones in children and provided prospects for future treatment options.


Assuntos
Nefrolitotomia Percutânea , Humanos , Criança , Nefrolitotomia Percutânea/métodos , Litotripsia/métodos , Cálculos Urinários/cirurgia , Cálculos Urinários/terapia , Cálculos Renais/cirurgia
3.
RSC Adv ; 14(28): 19912-19921, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38903665

RESUMO

Chromite ore processing residue (COPR) is a typical hazardous waste, which contains Cr(vi) and poses a great threat to the ecological environment and human health. In this study, solidification/stabilization (S/S) of COPR was carried out by using blast furnace slag (BFS) and fly ash (FA) to prepare alkali-activated cementitious materials (AACM). The influence of different factors (water glass modulus, liquid-solid ratio, alkali-solid content and curing temperature) on compressive strength was investigated by single-factor experiment. Additionally, solidification effect of AACM was determined according to the compressive strength and the leaching concentration of chromium (Cr(vi) and total Cr). According to the optimal conditions of the single-factor experiment, the highest compressive strength of 147.6 MPa was obtained after using the water glass modulus 1.0, liquid-solid ratio 0.28, alkali-solid content 8%, curing temperature 45 °C. The COPR was solidified in the AACM sample having highest compressive strength. The solidified body still has a good mechanical property (38.2 MPa) with 60% addition COPR. According to leaching tests, the leaching of Cr(vi) and total Cr of solidified body with 50% COPR was far lower than the limit value, which met the purpose of construction and landfill disposal. X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis proved that heavy metal chromium was solidified in AACM by physical and chemical means.

4.
Cell Death Dis ; 15(6): 437, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902257

RESUMO

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20-CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.


Assuntos
Quimiocina CCL20 , Neoplasias Colorretais , Células-Tronco Neoplásicas , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptores CCR6 , Transdução de Sinais , Linfócitos T Reguladores , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Ligante RANK/metabolismo , Receptores CCR6/metabolismo , Receptores CCR6/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Masculino , Camundongos , Feminino , Metástase Neoplásica , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Camundongos Nus , Movimento Celular
5.
Hepatol Int ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878111

RESUMO

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

6.
J Thorac Dis ; 16(4): 2654-2667, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38738242

RESUMO

Background and Objective: Obstructive sleep apnea (OSA) is a common chronic disorder characterized by repeated breathing pauses during sleep caused by upper airway narrowing or collapse. The gold standard for OSA diagnosis is the polysomnography test, which is time consuming, expensive, and invasive. In recent years, more cost-effective approaches for OSA detection based in predictive value of speech and snoring has emerged. In this paper, we offer a comprehensive summary of current research progress on the applications of speech or snoring sounds for the automatic detection of OSA and discuss the key challenges that need to be overcome for future research into this novel approach. Methods: PubMed, IEEE Xplore, and Web of Science databases were searched with related keywords. Literature published between 1989 and 2022 examining the potential of using speech or snoring sounds for automated OSA detection was reviewed. Key Content and Findings: Speech and snoring sounds contain a large amount of information about OSA, and they have been extensively studied in the automatic screening of OSA. By importing features extracted from speech and snoring sounds into artificial intelligence models, clinicians can automatically screen for OSA. Features such as formant, linear prediction cepstral coefficients, mel-frequency cepstral coefficients, and artificial intelligence algorithms including support vector machines, Gaussian mixture model, and hidden Markov models have been extensively studied for the detection of OSA. Conclusions: Due to the significant advantages of noninvasive, low-cost, and contactless data collection, an automatic approach based on speech or snoring sounds seems to be a promising tool for the detection of OSA.

7.
Aust Crit Care ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38580485

RESUMO

BACKGROUND: Intensive care unit (ICU) delirium is a common complication in older critically ill patients that has a significant impact. The Family Confusion Assessment Method (FAM-CAM) is a vital tool for assisting family members in identifying delirium; however, no study has yet been reported on the Chinese version of the scale. OBJECTIVES: The objective of this study was to translate the FAM-CAM into a Chinese version and to verify its effectiveness for delirium detection in an online patient visit setting. METHODS: This was a cross-sectional study. The FAM-CAM was translated to Chinese according to the International Society for Pharmacoeconomics and Outcomes Research guidelines. Patients and family members were recruited to participate in delirium assessments in three ICUs of one hospital. Family members then used the Chinese version of the FAM-CAM to assess for delirium via online visitation, and ICU nurses assessed patients for delirium using the Intensive Care Delirium Screening Checklist (ICDSC). Results were then compared between family members' and nurses' assessments. RESULTS: Overall, 190 critically ill patients and 190 family members were included, of whom 117 (61.6%) were assessed for delirium using the Intensive Care Delirium Screening Checklist. The Cohen's kappa coefficient between the Intensive Care Delirium Screening Checklist and FAM-CAM was 0.759 (P < 0.01). The sensitivity of the Chinese version of the FAM-CAM was 0.880, specificity was 0.890, positive predictive value was 0.928, negative predictive value was 0.823, and area under the receiver operating characteristic curve was 0.881 (95% confidence interval: 0.872-0.935, P < 0.01). CONCLUSION: The Chinese version of the FAM-CAM was shown to effectively help families detect delirium and was suggested as a crucial tool for assisting ICU nurses in the early identification of delirium. This tool may effectively be used to assess delirium during online visits.

8.
Front Microbiol ; 15: 1341303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572242

RESUMO

Understanding the interactions between fish gut microbiota and the aquatic environment is a key issue for understanding aquatic microorganisms. Environmental microorganisms enter fish intestines through feeding, and the amount of invasion varies due to different feeding habits. Traditional fish feeding habitat preferences are determined by fish morphology or behavior. However, little is known about how the feeding behavior of fish relative to the vertical structure in a shallow lake influences gut microbiota. In our study, we used nitrogen isotopes to measure the trophic levels of fish. Then high-throughput sequencing was used to describe the composition of environmental microbiota and fish gut microbiota, and FEAST (fast expectation-maximization for microbial source tracking) method was used to trace the source of fish gut microbiota. We investigated the microbial diversity of fish guts and their habitats in Lake Sanjiao and verified that the sediments indeed played an important role in the assembly of fish gut microbiota. Then, the FEAST analysis indicated that microbiota in water and sediments acted as the primary sources in half of the fish gut microbiota respectively. Furthermore, we classified the vertical habitat preferences using microbial data and significant differences in both composition and function of fish gut microbiota were observed between groups with distinct habitat preferences. The performance of supervised and unsupervised machine learning in classifying fish gut microbiota by habitat preferences actually exceeded classification by fish species taxonomy and fish trophic level. Finally, we described the stability of fish co-occurrence networks with different habitat preferences. Interestingly, the co-occurrence network seemed more stable in pelagic fish than in benthic fish. Our results show that the preferences of fish in the vertical structure of habitat was the main factor affecting their gut microbiota. We advocated the use of microbial interactions between fish gut and their surrounding environment to reflect fish preferences in vertical habitat structure. This approach not only offers a novel perspective for understanding the interactions between fish gut microbiota and environmental factors, but also provides new methods and ideas for studying fish habitat selection in aquatic ecosystems.

9.
Hepatobiliary Surg Nutr ; 13(2): 258-272, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617474

RESUMO

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

11.
Front Microbiol ; 15: 1374209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686106

RESUMO

Environmental temperature affects the composition, structure, and function of the gut microbial communities in host animals. To elucidate the role of gut microbiota in thermal adaptation, we designed a 2 species × 3 temperatures experiment, whereby we acclimated adult males of two agamid lizard species (warm-climate Leiolepis reevesii and cold-climate Phrynocephalus przewalskii) to 20, 28, and 36°C for 2 weeks and then collected their fecal and small-intestinal samples to analyze and compare the microbiota using 16S rRNA gene amplicon sequencing technology. The fecal microbiota displayed more pronounced interspecific differences in microbial community than the small-intestinal microbiota in the two species occurring in thermally different regions. The response of fecal and small-intestinal microbiota to temperature increase or decrease differed between the two species, with more bacterial taxa affected by acclimation temperature in L. reevesii than in P. przewalskii. Both species, the warm-climate species in particular, could cope with temperature change by adjusting the relative abundance of functional categories associated with metabolism and environmental information processing. Functional genes associated with carbohydrate metabolism were enhanced in P. przewalskii, suggesting the contribution of the fecal microbiota to cold-climate adaptation in P. przewalskii. Taken together, our results validate the two hypotheses tested, of which one suggests that the gut microbiota should help lizards adapt to thermal environments in which they live, and the other suggests that microbial communities should be thermally more sensitive in warm-climate lizards than in cold-climate lizards.

12.
Nano Lett ; 24(15): 4537-4545, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38568783

RESUMO

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

13.
J Phys Condens Matter ; 36(25)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38457834

RESUMO

A variety of distinct anisotropic exchange interactions commonly exist in one magnetic material due to complex crystal, magnetic and orbital symmetries. Here we investigate the effects of multiple anisotropic exchange interactions on topological magnon in a honeycomb ferromagnet, and find a chirality-selective topological magnon phase transition induced by a complicated interplay of Dzyaloshinsky-Moriya interaction and pseudo-dipolar interaction, accompanied by the bulk gap close and reopen with chiral inversion. Moreover, this novel topological phase transition involves band inversion at high symmetry pointsKandK', which can be regarded as a pseudo-orbital reversal, i.e. magnon valley degree of freedom, implying a new manipulation corresponding to a sign change of the magnon thermal Hall conductivity. Indeed, it can be realized in 4dor 5dcorrelated materials with both spin-orbit coupling and orbital localized states, such as iridates and ruthenates,etc.This novel regulation may have potential applications on magnon devices and topological magnonics.

14.
World J Psychiatry ; 14(2): 266-275, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38464776

RESUMO

BACKGROUND: Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening. Patients usually experience depression and anxiety, which affect their sleep quality and post-traumatic growth levels. AIM: To investigate the effects of sepsis, a one-hour bundle (H1B) management was combined with psychological intervention in patients with sepsis. METHODS: This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People's Hospital between June 2022 and June 2023. According to different intervention methods, the participants were divided into a simple group (SG, n = 150) and combined group (CG, n = 150). H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG. The changes of negative emotion, sleep quality and post-traumatic growth and prognosis were compared between the two groups before (T0) and after (T1) intervention. RESULTS: After intervention (T1), the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG (P < 0.001). Sleep time, sleep quality, sleep efficiency, daytime dysfunction, sleep disturbance dimension score, and the total score in the CG were significantly lower than those in the SG (P < 0.001). The appreciation of life, mental changes, relationship with others, personal strength dimension score, and total score of the CG were significantly higher than those of the SG (P < 0.001). The scores for mental health, general health status, physiological function, emotional function, physical pain, social function, energy, and physiological function in the CG were significantly higher than those in the SG (P < 0.001). The mechanical ventilation time, intensive care unit stay time, and 28-d mortality of the CG were significantly lower than those of the SG (P < 0.05). CONCLUSION: H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.

15.
mBio ; 15(5): e0034824, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38530034

RESUMO

A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization per se does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA. IMPORTANCE: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.


Assuntos
Proteínas do Capsídeo , Capsídeo , HIV-1 , Imunidade Inata , Proteínas de Membrana , Nucleotidiltransferases , Transcrição Reversa , HIV-1/genética , HIV-1/imunologia , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/imunologia , Capsídeo/metabolismo , Capsídeo/imunologia , Transdução de Sinais , Células HEK293 , Infecções por HIV/virologia , Infecções por HIV/imunologia , Infecções por HIV/genética , RNA Viral/genética , RNA Viral/metabolismo
16.
Medicine (Baltimore) ; 103(11): e37443, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489724

RESUMO

RATIONALE: Negative pressure pulmonary edema (NPPE) is an acute onset of non-cardiogenic interstitial pulmonary edema, commonly seen among surgical patients after extubation from general aneasthesia. It is mainly caused by rapid inspiration with acute upper airway obstruction resulting in significant negative thoracic pressure. PATIENT CONCERNS: A 24-year-old female patient who underwent laparoscopic cholecystectomy under general anesthesia and developed NPPE postoperatively. DIAGNOSES: Her main clinical manifestation was coughing up pink foamy sputum; postoperative CT showed increased texture in both lungs and bilateral ground glass opacities. INTERVENTIONS: Diuretics and steroids were used, and symptomatic supportive treatments such as oxygen were given. OUTCOMES: After treatment, on the fourth post-operative day, her symptoms were relieved and her vital signs were stable enough for her to be discharged. LESSONS: Although this is a rare and severe complication, the prognosis of NPPE is good when it is managed with proper diagnosis and treatment.


Assuntos
Obstrução das Vias Respiratórias , Colecistectomia Laparoscópica , Edema Pulmonar , Humanos , Feminino , Adulto Jovem , Adulto , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Colecistectomia Laparoscópica/efeitos adversos , Diuréticos/uso terapêutico , Oxigênio , Anestesia Geral/efeitos adversos , Obstrução das Vias Respiratórias/complicações
17.
J Gastrointest Oncol ; 15(1): 468-477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482229

RESUMO

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

18.
J Gastrointest Oncol ; 15(1): 458-467, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482250

RESUMO

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

19.
ACS Nano ; 18(8): 6673-6689, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353701

RESUMO

The current live rotavirus (RV) vaccines show reduced effectiveness in developing countries, calling for vaccine strategies with improved efficacy and safety. We generated pseudovirus nanoparticles (PVNPs) that display multiple ectodomains of RV viral protein 4 (VP4), named S-VP4e, as a nonreplicating RV vaccine candidate. The RV spike protein VP4s that bind host receptors and facilitate viral entry are excellent targets for vaccination. In this study, we developed scalable methods to produce three S-VP4e PVNPs, each displaying the VP4e antigens from one of the three predominant P[8], P[4], and P[6] human RVs (HRVs). These PVNPs were recognized by selected neutralizing VP4-specific monoclonal antibodies, bound glycan receptors, attached to permissive HT-29 cells, and underwent cleavage by trypsin between VP8* and VP5*. 3D PVNP models were constructed to understand their structural features. A trivalent PVNP vaccine containing the three S-VP4e PVNPs elicited high and well-balanced VP4e-specific antibody titers in mice directed against the three predominant HRV P types. The resulting antisera neutralized the three HRV prototypes at high titers; greater than 4-fold higher than the neutralizing responses induced by a trivalent vaccine consisting of the S60-VP8* PVNPs. Finally, the trivalent S-VP4e PVNP vaccine provided 90-100% protection against diarrhea caused by HRV challenge. Our data supports the trivalent S-VP4e PVNPs as a promising nonreplicating HRV vaccine candidate for parenteral delivery to circumvent the suboptimal immunization issues of all present live HRV vaccines. The established PVNP-permissive cell and PVNP-glycan binding assays will be instrumental for further investigating HRV-host cell interactions and neutralizing effects of VP4-specific antibodies and antivirals.


Assuntos
Rotavirus , Vacinas Virais , Animais , Camundongos , Humanos , Nanovacinas , Proteínas Virais/metabolismo , Anticorpos Neutralizantes , Polissacarídeos , Imunidade , Anticorpos Antivirais
20.
Curr Med Chem ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38415439

RESUMO

INTRODUCTION: Due to the confounding heterogeneity, the therapeutic strategy for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) remains to be defined. CASE REPRESENTATION: We report a 38-year-old man with recurrent swelling of the eyelids and lower limbs, undergoing rituximab combined with steroid and tacrolimus treatment, who achieved an improved renal outcome. Underlying solid malignant tumours were excluded from the diagnosis. DISCUSSION: We treated patients with rituximab along with steroids and tacrolimus. Improvements in proteinuria and renal function were observed. We also reviewed the current literature to assess the efficacy of rituximab in the treatment of PGNMID. CONCLUSION: However, a larger pool of patients and a longer follow-up period are required to establish the role of rituximab and steroids in the treatment of PGNMID.

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