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Highlights A 2.5-dimensional dynamic structural color based on nanogratings of heterogeneous materials was proposed by interweaving a pH-responsive hydrogel with IP-L photoresist. The nanogrid structures exhibit brilliant tuneable structural color, high sensitivity, and ultrafast recovery speeds in response to pH. The 4D printing-based grayscale design approach was proposed for the patterned encoding and array printing of dynamic structural colors, promoting their application in patterned printing, information encryption, and microfluidic chip sensing.

Aim of the StudyTo study the changes in the chemical composition and medicinal effects of black ginseng during processing.Materials and MethodsThe contents of ginsenosides Rg1, Re, Rh1, Rb1, 20-(S)-Rg3, 20-(R)-Rg3, and Rg5 were determined using high-performance liquid chromatography (HPLC), and the percentage of rare saponins was calculated. Furthermore, changes in the contents of reducing sugars and amino acids (i.e., Maillard reaction (MR) substrates) were measured to assess the relationship between processing and the MR. Compounds were identified using HPLC-MS and their cleavage patterns were analyzed. Gene co-expression network bioinformatics techniques were applied to identify the pharmacological mechanism of black ginseng.ResultsThe changes in the physicochemical characteristics of black ginseng during processing were determined based on the MR. Rare saponins accumulated during black ginseng processing. In addition, reducing sugars were produced through polysaccharide pyrolysis and the MR; thus, their content initially increased and then decreased. The amino acid content gradually decreased as the number of evaporation steps increased, indicating that both amino acids and reducing sugars acted as substrates for the MR during black ginseng processing. Thirty-one saponins, 18 sugars, and 58 amino acids were identified based on the MS analysis. Transcriptomics results demonstrated that black ginseng can regulate signaling pathways such as the TNF, IL-17, MAPK, and PI3K-Akt pathways. This finding helps us understand the observed proliferation and differentiation of immune-related cells and positively regulated cell adhesion.

Human parechovirus (HPeV) is a common virus that can cause severe infections in newborns. Due to the limited knowledge of the prevalence of HPeV in different cities in China and the unknown association between HPeV infection and clinical characteristics of newborns, this research investigated the epidemiological and clinical characteristics of HPeV infection in hospitalized neonates in Changsha. From August to October 2023, 145 anal swab samples from 96 newborns and 38 pharyngeal swab samples from 33 newborns in the neonatal intensive care unit (NICU) were collected. The prevalence of HPeV was detected by reverse transcription-polymerase chain reaction (RT-PCR). The genomes of HPeV were sequenced and the viral protein 1 (VP1) region was used for genotyping. Phylogenetic analysis and recombination analysis of HPeV genome were performed. Finally, HPeV was detected in 10 out of 44 patients in October, all of them were HPeV-1. The sequenced 4 genomes of HPeV showed high genetic diversity with known strains. Additionally, a HPeV-1 recombinant strain was detected. Compared with HPeV negative patients, HPeV patients had higher prevalence of abdominal pain and diarrhea, intracranial hemorrhage, and purulent meningitis. Compared with HPeV negative patients, HPeV patients had higher peripheral blood lymphocytes, albumin, globulin, pH and lower peripheral blood neutrophils and hemoglobin. HPeV is an important viral cause of newborn infections and appears to be increasing in prevalence in recent years. Characteristic clinical pictures exist in HPeV infections, and further research is needed to accumulate more cases to obtain a comprehensive understanding of HPeV infections.

IntroductionThis study aimed to investigate the virome diversity of the SLE disease and the association between viral infections and the disease.MethodsSLE-related RNA-Seq data were retrieved from public databases. A rigorous computational workflow was employed to identify the human viruses. Differential expression analysis and functional enrichment analysis were conducted in R.ResultsWe identified ten human virus species from 826 RNA-Seq samples of human blood, comprising 688 SLE patients and 138 healthy controls. Eight of the ten virus species exhibited higher positive rates in SLE patients compared to healthy controls, with Human betaherpesvirus 5 (HHV5) having the highest positive rate (4.1%) and being exclusively detected in SLE samples. The virus abundances were low and comparable in both SLE patients and healthy controls. Analysis of the antiviral interferon-stimulated genes (ISGs) in samples showed higher ISG expression levels in HHV4 and HHV5-positive samples compared to virus-negative samples. Several genes that were up-regulated in SLE patients were further up-regulated after HHV5 infection, and they were mainly enriched in immune response-related biological processes. Additionally, the expression levels of several marker genes of SLE severity were compared between HHV5-positive and virus-negative SLE patients, suggesting that HHV5 infection may be associated with aggravated SLE disease.DiscussionWe found that SLE patients are more susceptible to viral infections than healthy individuals. Viral infections, such as HHV5, may be associated with aggravated SLE disease. This study deepens our understanding of the association between viruses and SLE and provides new insights into prevention and control of the disease.

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens.IMPORTANCEOur study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

The liver plays a crucrial role in detoxification, metabolism, and nutrient storage. Because liver cancer ranks among the top three leading causes of death globally, there is an urgent need for developing treatment strategies for liver cancer. Although traditional approaches such as radiation, chemotherapy, surgical removal, and transplantation are widely practiced, the number of patients with liver cancer continues to increase rapidly each year. Some novel therapeutics for liver cancer have been studied for many years. In the past decade, oncolytic therapy has emerged, in which viruses selectively infect and destroy cancer cells while sparing normal cells. However, oncolytic virotherapy for liver cancer remains relatively obscure due to the aggressive nature of the disease and the limited effectiveness of treatment. To keep pace with the latest developments in oncolytic tumor therapy for liver cancer, this review summarizes basic science studies and clinical trials conducted within 5 years, focusing on the efficacy and safety profiles of the five most commonly used oncolytic viruses: herpes simplex virus, adenovirus, influenza virus, vaccinia virus, and coxsackievirus.

Recent advancements in constructed wetlands (CWs) have highlighted the imperative of enhancing nitrogen (N) removal efficiency. However, the variability in influent substrate concentrations presents a challenge in optimizing N removal strategies due to its impact on removal efficiency and mechanisms. Here we show the interplay between influent substrate concentration and N removal processes within integrated vertical-flow constructed wetlands (IVFCWs), using wastewaters enriched with NO3−-N and NH4+-N at varying carbon to nitrogen (C/N) ratios (1, 3, and 6). In the NO3−-N enriched systems, a positive correlation was observed between the C/N ratio and total nitrogen (TN) removal efficiency, which markedly increased from 13.46 ± 2.23% to 87.00 ± 2.37% as the C/N ratio escalated from 1 to 6. Conversely, in NH4+-N enriched systems, TN removal efficiencies in the A-6 setup (33.69 ± 4.83%) were marginally 1.25 to 1.29 times higher than those in A-3 and A-1 systems, attributed to constraints in dissolved oxygen (DO) levels and alkalinity. Microbial community analysis and metabolic pathway assessment revealed that anaerobic denitrification, microbial N assimilation, and dissimilatory nitrate reduction to ammonium (DNRA) predominated in NO3−-N systems with higher C/N ratios (C/N ≥ 3). In contrast, aerobic denitrification and microbial N assimilation were the primary pathways in NH4+-N systems and low C/N NO3−-N systems. A mass balance approach indicated denitrification and microbial N assimilation contributed 4.12–47.12% and 8.51–38.96% in NO3−-N systems, respectively, and 0.55–17.35% and 7.83–33.55% in NH4+-N systems to TN removal. To enhance N removal, strategies for NO3−-N dominated systems should address carbon source limitations and electron competition between denitrification and DNRA processes, while NH4+-N dominated systems require optimization of carbon utilization pathways, and ensuring adequate DO and alkalinity supply.

Urban surface water pollution poses significant threats to aquatic ecosystems and human health. Conventional nitrogen removal technologies used in urban surface water exhibit drawbacks such as high consumption of carbon sources, high sludge production, and focus on dissolved oxygen (DO) concentration while neglecting the impact of DO gradients. Here, we show an ecological filter walls (EFW) that removes pollutants from urban surface water. We utilized a polymer-based three-dimensional matrix to enhance water permeability, and emergent plants were integrated into the EFW to facilitate biofilm formation. We observed that varying aeration intensities within the EFW's aerobic zone resulted in distinct DO gradients, with an optimal DO control at 3.19 ± 0.2 mg L−1 achieving superior nitrogen removal efficiencies. Specifically, the removal efficiencies of total organic carbon, total nitrogen, ammonia, and nitrate were 79.4%, 81.3%, 99.6%, and 79.1%, respectively. Microbial community analysis under a 3 mg L−1 DO condition revealed a shift in microbial composition and abundance, with genera such as Dechloromonas, Acinetobacter, unclassified_f__Comamonadaceae, SM1A02 and Pseudomonas playing pivotal roles in carbon and nitrogen elimination. Notably, the EFW facilitated shortcut nitrification-denitrification processes, predominantly contributing to nitrogen removal. Considering low manufacturing cost, flexible application, small artificial trace, and good pollutant removal ability, EFW has promising potential as an innovative approach to urban surface water treatment.

Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient. In this study, we identified two subgroups with distinct senescent clusters among geriatric breast cancer patients through multi-omics analysis. Using various machine learning algorithms, we developed a comprehensive scoring model called “Sene_Signature,” which more accurately distinguished elderly breast cancer patients compared with existing methods and better predicted their prognosis. The Sene_Signature was correlated with tumor immune cell infiltration, as supported by single-cell transcriptomics, RNA sequencing, and pathological data. Furthermore, we observed increased drug responsiveness in patients with a high Sene_Signature to treatments targeting the epidermal growth factor receptor and cell-cycle pathways. We also established a user-friendly web platform to assist investigators in assessing Sene_Signature scores and predicting treatment responses for elderly breast cancer patients. In conclusion, we developed a novel model for evaluating prognosis and therapeutic responses, providing a potential molecular classification that assists in the pre-treatment assessment of geriatric breast cancer.

ABSTRACTThe vaccination rate for seasonal influenza remains low in most regions of China. It is essential to understand the factors that associated with the low influenza vaccination rate in various populations after the COVID-19 pandemic. A cross-sectional survey was conducted with residents in Pudong New Area, Shanghai, China. Respondents’ vaccination condition during the 2021–2022 flu season and the reasons for receiving or not receiving influenza vaccine were investigated. Binary logistic regression was conducted to explore potential factors influencing vaccination uptake. 2,476 of 14,001 respondents received an influenza vaccine, with a total coverage of 17.68% (95% CI: 17.05%, 18.32%). Children had the highest vaccination coverage (35.68%; 95% CI: 34.02, 37.33), followed by adults (12.75%; 95% CI: 11.91%, 13.58%) and elderly individuals (11.70%, 95% CI: 10.78%, 12.62%). For children, lower household income was an significant promoting factor. For adults, factors significantly associated with vaccination were household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P

BackgroundNirmatrelvir-ritonavir (Paxlovid) has received emergency use authorization from the US Food and Drug Administration owing to its effectiveness and safety. However, data on the effectiveness and safety of Paxlovid use in COVID-19 patients with onset of more than 5 days are lacking.MethodsA real-world retrospective study was performed during the outbreak involving the SARS-CoV-2 BA.5.2 subvariant. Hospitalized COVID-19 patients (including mild, moderate, severe and critical cases) were divided into three groups: Paxlovid treatment within (Group A) or more than (Group B) 5 days of COVID-19 onset and no Paxlovid treatment during more than 5 days of COVID-19 onset with only basic symptomatic treatment (Group C). Endpoints were all-cause 28-day mortality, improvement in clinical classification, and a composite endpoint of disease progression, viral load and virus elimination time. Safety was assessed by comparing adverse events reported during treatment in each group.ResultsDuring the period, 248 hospitalized COVID-19 patients, including 55 in Group A, 170 in Group B, and 23 in Group C, were enrolled. There were no significant differences in the clinical classification improvement rate [80.0% (16/20) vs. 81.3% (52/64), p = 1.000; 60.0% (21/35) vs. 55.7% (59/106), p = 0.653, respectively] or all-cause 28-day mortality [0% (0/20) vs. 1.6% (1/64), p = 1.000; 11.4% (4/35) vs. 6.6% (7/106), p = 0.576, respectively] between Groups A and B for nonsevere and severe cases. However, the clinical classification improvement rate in Group B was markedly higher than that in Group C [81.3% (52/64) vs. 50.0% (6/12), p = 0.049] among nonsevere cases. Cycle threshold values of the N and ORF genes in Group B were significantly increased after Paxlovid treatment [31.14 (IQR 26.81–33.93) vs. 38.14 (IQR 36.92–40.00), p < 0.001; 31.33 (IQR 26.00–33.47) vs. 38.62 (IQR 35.62–40.00), p < 0.001, respectively]. No significant differences in reported adverse events of neurological disease (p = 0.571), liver injury (p = 0.960) or kidney injury (p = 0.193) between Group A and Group B were found.ConclusionPaxlovid treatment within 10 days of onset can shorten the disease course of COVID-19 by reducing the viral load. Paxlovid is effective and safe in treating COVID-19 with onset of more than five or even 10 days when patients have a high viral load.

To realize nanoscale manufacturing based on laser direct writing technology, objective lenses with high numerical apertures immersed in water or oil are necessary. The use of liquid medium restricts its application in semiconductors. Achieving nanoscale features on silicon by laser direct writing in a low refractive index medium has been a challenge. In this work, a microsphere assisted femtosecond laser far-field induced dewetting approach is proposed. A reduction in the full-width at half-maximum of the focused light spot is realized by modulating tightly focused light through microspheres and achieving a minimum feature size of 9 nm on silicon in ambient air with energy smaller than the ablation threshold. Theoretical analysis and numerical simulation of laser processing are performed based on a two-temperature model. Furthermore, we explored the potential of femtosecond laser-induced dewetting in nanolithography and demonstrated its ability to achieve an arbitrary structure on silicon. Our work enables laser-based far-field sub-10-nm feature etching on a large-scale, providing a novel avenue for nanoscale silicon manufacturing.

Abstract Background/Objective With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. Methods A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. Result The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). Conclusion Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

ABSTRACTAnti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.

Pulsed Electric Fields (PEF) technology is an emerging non-thermal food processing technology that is widely used because of its low damage to food quality and its ability to kill harmful microorganisms in food. The oxidative stress caused by PEF results in the synthesis and accumulation of nutrients, and plant foods stimulated by PEF produce large amounts of Reactive Oxygen Species (ROS), which activate the metabolite synthesis pathway and eventually synthesize proteins, polyphenols, thioglucosides and carotenoids; ROS accumulate in the cell membrane of microorganisms and cause protein expression. The accumulation of ROS in the cell membrane of microorganisms can cause abnormal protein expression, damage the lipid layer and Deoxyribonucleic Acid (DNA), and eventually lead to microbial inactivation. PEF technology in food processing are multifaceted, enhancing both the nutritional value of food through the augmented presence of health-beneficial compounds and ensuring food safety by effectively inactivating harmful microorganisms. This innovative technology stands at the forefront of food processing solutions, promising to fulfill the growing consumer demand for foods that are not only safe and of high quality but also rich in nutritional value. PEF’s role as a cornerstone technology in the food industry heralds a new era of food processing, where nutrition and safety converge to meet the sophisticated needs of today’s consumers.

BackgroundThe prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection.MethodsThis retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients.ResultsThe sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p

Abstract Background Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA. Methods We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks’ funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I 2 statistic were used to test the heterogeneity. Results Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks’s test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value

Coronaviruses (CoVs), the largest positive-sense RNA viruses, have caused infections in both humans and animals. The cross-species transmission of CoVs poses a serious threat to public health. Rodents and bats, the two largest orders of mammals, serve as significant natural reservoirs for CoVs. It is important to monitor the CoVs carried by bats and rodents. In this study, we collected 410 fecal samples from bats and 74 intestinal samples from rats in Yunnan Province, China. Using RT-PCR, we identified one positive sample for alphacoronavirus (TC-14) from Rhinolophus sinicus (Chinese rufous horseshoe bat) and two positive samples for betacoronavirus (GS-53, GS-56) from Apodemus ilex (Rodentia: Muridae). We successfully characterized the complete genomes of TC-14 and GS-56. Phylogenetic analysis revealed that TC-14 clustered with bat CoV HKU2 and SADS-CoV, while GS-56 was closely related to rat CoV HKU24. The identification of positive selection sites and estimation of divergence dates further helped characterize the genetic evolution of TC-14 and GS-56. In summary, this research reveals the genetic evolution characteristics of TC-14 and GS-56, providing valuable references for the study of CoVs carried by bats and rodents in Yunnan Province.

Pyroptosis, known as one typical mode of programmed cell death, is generally characterized by the cleaved gasdermin family (GSDMs) forming pores in the cell membrane and inducing cell rupture, and the activation of aspartate-specific proteases (caspases) has also been found during this process. Diabetic Kidney Disease (DKD) is caused by the complication of diabetes in the kidney, and the most important kidney’s function, Glomerular Filtration Rate (GFR), happens to drop to less than 90% of its usual and even lead to kidney failure in severe cases. The persistent inflammatory state induced by high blood glucose implies the key pathology of DKD, and growing evidence shows that pyroptosis serves as a significant contributor to this chronic immune-mediated inflammatory disorder. Currently, the expanded discovery of GSDMs, pyroptosis, and its association with innate immunity has been more attractive, and overwhelming research is needed to sort out the implication of pyroptosis in DKD pathology. In this review, we comb both classical studies and newly founds on pyroptosis, prick off the novel awakening of pyroptosis in DKD, and center on the significance of pyroptosis in DKD treatment, aiming to provide new research targets and treatment strategies on DKD.

Abstract Liquid metal (LM) exhibits a distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state, thus it is considered a promising material for high-performance soft electronics. However, rapid patterning LM to achieve a sensory system with high sensitivity remains a challenge, mainly attributed to the poor rheological property and wettability. Here, we report a rheological modification strategy of LM and strain redistribution mechanics to simultaneously simplify the scalable manufacturing process and significantly enhance the sensitivity of LM sensors. By incorporating SiO2 particles into LM, the modulus, yield stress, and viscosity of the LM-SiO2 composite are drastically enhanced, enabling 3D printability on soft materials for stretchable electronics. The sensors based on printed LM-SiO2 composite show excellent mechanical flexibility, robustness, strain, and pressure sensing performances. Such sensors are integrated onto different locations of the human body for wearable applications. Furthermore, by integrating onto a tactile glove, the synergistic effect of strain and pressure sensing can decode the clenching posture and hitting strength in boxing training. When assisted by a deep-learning algorithm, this tactile glove can achieve recognition of the technical execution of boxing punches, such as jab, swing, uppercut, and combination punches, with 90.5% accuracy. This integrated multifunctional sensory system can find wide applications in smart sport-training, intelligent soft robotics, and human-machine interfaces.

Objectives: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians. Methods: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022. Results: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative. Conclusion: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative.

The solar wind has been extensively studied recently with in situ observations, and the understanding of its counterpart near the solar surface has also progressed significantly. With the spectroscopic observations from the Chinese H α Solar Explorer (CHASE), the chromospheric Dopplergram of the full solar disk is first obtained almost simultaneously. By investigating the statistics of the Doppler velocities at the chromosphere, we find that the coronal hole (CH) regions are dominated by Doppler blueshifts, with a stronger net magnetic flux region corresponding to smaller blueshift velocity. In addition to the average blueshift, the probability density of the Doppler shift is not symmetrically distributed but shows an excess at the redshift side, while the reference region does not show such an asymmetry. The redshift asymmetry may provide a possible clue for the interchange reconnection that might happen just above the chromosphere. By sampling the regions at the network boundaries in the CHs, the probability density is slightly enhanced at the parts of both larger blueshifts and redshifts compared with the result for the whole CH region. As the reference region also shows such enhancement, the crucial area associated with the origin of solar wind is not identified efficiently by sampling the overall network boundaries as demonstrated here. The present study shows the first attempt at interpreting the origin of solar wind in the transient CHs based on the CHASE spectroscopic observations, and a combination of full-disk and high-resolution observations is helpful in the future for firmly understanding the source region of solar wind.

Solar prominences observed close to the limb commonly include a bright feature that, from the perspective of the observer, runs along the interface between itself and the underlying chromosphere. Despite several idealized models being proposed to explain the underlying physics, a more general approach remains outstanding. In this manuscript we demonstrate as a proof of concept the first steps in applying the Lightweaver radiative transfer framework’s 2.5D extension to a “toy” model prominence + VAL3C chromosphere, inspired by recent 1.5D experiments that demonstrated a significant radiative chromosphere–prominence interaction. We find the radiative connection to be significant enough to enhance both the electron number density within the chromosphere, as well as its emergent intensity across a range of spectral lines in the vicinity of the filament absorption signature. Inclining the viewing angle from the vertical, we find these enhancements to become increasingly asymmetric and merge with a larger secondary enhancement sourced directly from the prominence underside. In wavelength, the enhancements are then found to be the largest in both magnitude and horizontal extent for the spectral line cores, decreasing into the line wings. Similar behavior is found within new Chinese H α Solar Explorer/H α Imaging Spectrograph observations, opening the door for subsequent statistical confirmations of the theoretical basis we develop here.

The eruption of solar filaments, also known as prominences appearing off limb, is a common phenomenon in the solar atmosphere. It ejects massive plasma and high-energy particles into interplanetary space, disturbing the solar-terrestrial environment. It is vital to obtain the three-dimensional velocity fields of erupting filaments for space-weather predictions. We derive the three-dimensional kinematics of an off-limb prominence and an on-disk filament, respectively, using the full-disk spectral and imaging data detected by the Chinese H α Solar Explorer (CHASE). It is found that both the prominence and the filament experience a fast semicircle-shaped expansion at first. The prominence keeps propagating outward with an increasing velocity until escaping successfully, with the south leg of the prominence finally moving back to the Sun in a swirling manner. For the filament, the internal plasma falls back to the Sun in a counterclockwise rotation in the late ejection, matching the failed eruption without a coronal mass ejection. During the eruptions, both the prominence and the filament show material splitting along the line-of-sight direction, revealed by the bimodal H α spectral profiles. For the prominence, the splitting begins at the top and gradually spreads to almost the whole prominence with a fast blueshift component and a slow redshift component. The material splitting in the filament is more fragmental. As shown by the present results, the CHASE full-disk spectroscopic observations make it possible to systematically study the three-dimensional kinematics of solar filament eruptions.

AbstractObjectives Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis.Methods Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed.Results Nineteen patients were enrolled, with a median age of 52 years (45–62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died.Conclusions T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.

Objectives: Localized or disseminated infection caused by different nontuberculous mycobacteria (NTM) species has been increasingly reported in recent years, but reports of Mycobacterium colombiense infection are extremely rare. Herein, we analyzed the clinical features of patients with disseminated M. colombiense infection. Methods: Patients diagnosed with disseminated M. colombiense infection between February 4, 2016 and August 25, 2021 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. Results: NTM infection was diagnosed in 248 HIV-negative patients. Of these, nine patients with disseminated M. colombiense infection were enrolled. Five of these patients were positive for anti-interferon-γ autoantibodies. The lung, lymph nodes, bones, and joints were the most commonly involved organs. Anemia, fever, lymphadenopathy, cough and expectoration, and ostealgia were the most common symptoms. The levels of white blood cells and neutrophils were increased in eight patients. M. colombiense was detected by both metagenomic next-generation sequencing (mNGS) and culture in four patients and only by mNGS in the remaining five patients. All patients received combination anti-NTM therapy; five underwent surgery. The condition of eight patients improved, and one died during the treatment. Conclusion: Patients infected with M. colombiense can present as disseminated infections, easily involving multiple organs, such as the lung, lymph nodes, bone, and joints, with fever, lymphadenopathy, and increased white blood cell and neutrophil counts. mNGS plays a crucial role in the early diagnosis of M. colombiense infection. Once diagnosed, timely and effective anti-NTM therapy, combined with local surgery if necessary, can improve the prognosis of patients with this condition.

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 μg∙mL−1) and EB (50, 100, and 150 μg∙mL−1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism.

Lodderomyces elongisporus, a rare emerging pathogen, can cause fungemia often related to immunosuppression or intravenous devices. Herein, we report the case of a 58-year-old woman with subacute infective endocarditis due to Lodderomyces elongisporus identified by blood fungal culture and whole-genome sequencing, who was treated with antifungals, mitral replacement and endocardial vegetation removal surgery.

Aims: The purpose of this study was to establish and verify a nomogram to predict the prognosis of patients with human immunodeficiency virus (HIV)-related talaromycosis marneffei and evaluate the prognosis. Methods: We examined the acquired immune deficiency syndrome (AIDS) patients hospitalized in the Fourth People's Hospital of Nanning from 2018 to 2020 with an aetiological diagnosis of Talaromyces marneffei infection. Logistic regression analysis was used to identify the independent risk factors for relapse or death of the prognosis of Talaromyces marneffei infection. According to the regression coefficient, the corresponding nomograph prediction model was drawn. Results: A total of 400 patients were included, including 321 males and 79 females. Recurrence or death occurred in 70 cases (17.5%). The area under the receiver operator characteristic curve (ROC) of the established model was 0.716 with good discrimination, calibration, and clinical effectiveness. The risks of age between 45 and 60 years old and 60 years old, and the risks of G test 100 pg/ml were higher than that of 50–100 pg/ml. Respiratory failure, decreased albumin and elevated total bilirubin are risk factors for relapse or death in HIV patients infected with Talaromyces marneffei. Conclusion: This model can accurately predict the prognosis of HIV complicated with Talaromyces marneffei infection.

ObjectiveThe incidence of non-alcoholic fatty liver disease is increasing every year, and there is growing evidence that metabolites and intestinal bacteria play a causal role in NAFLD. Gentiopicroside, a major iridoids compound in gentian, has been reported to reduce hepatic lipid accumulation. However to date, no studies have confirmed whether the predominance of Gentiopicroside is related to metabolites and intestinal bacteria. Therefore, we sought to study whether the hypolipidemic effect of Gentiopicroside is related to metabolic function and intestinal flora regulation.MethodsIn the present study, C57BL/6J mice were fed a high-fat diet for 12 weeks, followed by a high-fat diet with or without Gentiopicroside for 8 weeks, respectively. The Gentiopicroside intervention reduced body weight gain, liver index, and decreased serum biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, and triglycerides in high-fat fed mice. The effect of Gentiopicroside on non-alcoholic fatty liver disease was studied using serum untargeted metabolomics and 16S rDNA assay.ResultsMetabolomic analysis showed that the addition of Gentiopicroside significantly altered the levels of amino acids, unmetabolized Gentiopicroside after administration, and metabolites such as Cinnoline, Galabiosylceramide, and Tryptophyl-Tyrosine, which are involved in the pathways regulating bile secretion, tryptophan metabolism, and lipid metabolism. Analysis of intestinal bacteria showed that Gentiopicrosides altered the community composition structure of intestinal bacteria, characterized by an increase and a decrease in beneficial and harmful bacteria, respectively. In addition, correlation analysis showed that the effect of Gentiopicroside on metabolites was positively correlated with intestinal flora Bacteroides, Lactobacillus, Muribaculum, and Prevotellaceae_UCG_001. Finally, the combined analysis revealed that metabolites were associated with the regulation of Firmicutes and Actinobacteria and positively correlated with lipid levels.ConclusionThese results suggest that Gentiopicroside may be a potential agent for the prevention of intestinal disorders and the alleviation of non-alcoholic fatty liver disease.

This paper presents three distinct wave trains that occurred on 2023 April 21: a broad quasiperiodic fast-propagating (QFP) wave train and bidirectional narrow QFP wave trains. The broad QFP wave train expands outward in a circular wave front, while bidirectional narrow QFP wave trains propagate in the northward and southward directions, respectively. The concurrent presence of the wave trains offers a remarkable opportunity to investigate their respective triggering mechanisms. Measurement shows that the speed of the broad QFP wave train is in the range of 300–1100 km s ^−1 in different propagating directions. There is a significant difference in the speed of the bidirectional narrow QFP wave trains: the southward propagation achieves 1400 km s ^−1 , while the northward propagation only reaches about 550 km s ^−1 accompanied by a deceleration of about 1–2 km s ^−2 . Using the wavelet analysis, we find that the periodicity of the propagating wave trains in the southward and northward directions closely matches the quasiperiodic pulsations exhibited by the flares. Based on these results, the narrow QFP wave trains were most likely excited by the intermittent energy release in the accompanying flare. In contrast, the broad QFP wave train had a tight relationship with the erupting filament, probably attributed to the unwinding motion of the erupting filament, or the leakage of the fast sausage wave train inside the filament body.

Abstract Tactile sensing is essentially required for dexterous manipulation in robotic applications. Mimicking human perception of softness identification in a non-invasive fashion, thus achieving satisfactory interaction with fragile objects remains a grand challenge. Here, a scatheless measuring methodology based on the multisensory electronic skins to quantify the elastic coefficient of soft materials is reported. This recognition approach lies in the preliminary classification of softness by piezoelectric signals with a modified machine learning algorithm, contributing to an appropriate contact force assignment for subsequent quantitative measurements via strain sensing feedback. The integration of multifunctional sensing system allows the manipulator to hold capabilities of self-sensing and adaptive grasping motility in response to objects with the various softness (i.e., kPa-MPa). As a proof-of-concept demonstration, the biomimetic manipulator cooperates with the robotic arm to realize the intelligent sorting of oranges varying in freshness, paving the way for the development of microsurgery robots, human-machine interfacing, and advanced prosthetics.

Abstract We investigated the clinical features and screened for predictive factors of anti-interferon-γ autoantibody (AIGA) positivity. We enrolled 63 AIGA-positive (group 1) and 29 AIGA-negative (group 2) HIV-negative patients. White blood cell (WBC) and neutrophil counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), globulin, immunoglobulin (Ig) G, and IgM levels were higher, whereas CD4+T cell count and hemoglobin level were lower in group 1 than in group 2. Co-infections, multiple infections, and disseminated infections were significantly higher in group 1 than in group 2. Prognosis was worse in group 1 than in group 2, especially for relapse and persistent infections. The number of infecting pathogens and sites involved; WBC and neutrophil counts; globulin, IgG, IgM, and CRP levels; and ESR were significantly positively correlated with AIGA titers; however, CD4+T cell count was significantly negatively correlated with AIGA titers. Therefore, IgG, globulin, and CRP levels; CD4+T cell and WBC counts; the number of infecting pathogens and sites involved; and ESR were considered potential predictors for AIGA positivity. For HIV-negative hosts with double or multiple opportunistic, disseminated infections and high serum IgG and globulin levels, low CD4+T cell count, and an increase in inflammatory marker levels, positive AIGA-associated immunodeficiency should be considered.

Background: Alcohol abuse leads to alcoholic liver disease (ALD), for which no effective treatment is yet known. Gentiana Scabra Bge is a traditional Chinese medicine; its extract has a significant liver protection effect, but its effects on the mechanism of improving alcohol-induced toxicity remain unclear. Therefore, this study used cell and mouse models to investigate how Gentiana Scabra Bge extract (GSE) might affect the TLT4/NF-κB inflammation pathway in ALD. Methods: In mice, we induced the alcoholic liver injury model by applying alcohol and induced the inflammatory cell model by lipopolysaccharide (LPS)-induced macrophages. Using an enzyme-linked immunosorbent assay (ELISA) kit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured in liver tissue; we also performed histological analysis of liver tissue sections to assess the hepatoprotective effect of GSE on alcohol. Using real-time fluorescence quantification, we determined the expression of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA levels; we used Western blotting to detect the expression of TLR4/NF-κB signaling pathway-related proteins. Results: We demonstrate that GSE decreased AST and ALT activity, ameliorated liver dysfunction, decreased cytokine levels, and reduced LPS-induced cellular inflammation. In addition, GSE protected mouse liver cells from the inflammatory response by reducing alcohol-induced liver pathological damage and downregulating genes and proteins such as nuclear factors. Conclusions: GSE can attenuate liver injury in mice through the TLR4/NF-κB pathway by inhibiting the activation of nuclear factors.

Abstract Background High-titer anti-interferon (IFN)-γ autoantibodies are strongly associated with intracellular pathogens such as nontuberculous mycobacteria and Talaromyces marneffei, but they are not as commonly associated with Talaromyces marneffei co-infected with Mycobacterium tuberculosis. Case presentation Herein, we report a case of an HIV-negative Chinese man with a severe, disseminated co-infection of Talaromyces marneffei and Mycobacterium tuberculosis, who had a high-titer of anti IFN-γ autoantibodies and a CFI heterozygous nonsense gene mutation. The patient rapidly developed sepsis and died. Through by flow cytometry for CD4+ T cells’ intracellular phosphorylated STAT-1 and Th1 cells (CD4+ IFN-γ+ cells), we found that the patient’s serum can inhibited IFN γ-induced CD4+ T cells’ STAT-1 phosphorylation and Th1 cell differentiation in normal peripheral blood mononuclear cells, but this phenomenon was not observed in normal control’s serum. In addition, the higher serum concentration in the culture medium, the more obvious inhibition of Th1 cell differentiation. Conclusions For HIV-negative individuals with relapsing, refractory, fatal double or multiple intracellular pathogen infections, especially Talaromyces marneffei, clinicians should be aware that if they might be dealing with adult-onset immunodeficiency syndrome due to high-titer anti-IFN-γ autoantibodies. Systematic genetic and immunological investigations should also be performed.

The heating mechanisms of solar white-light flares remain unclear. We present an X1.0 white-light flare on 2022 October 2 (SOL2022-10-02T20:25) observed by the Chinese H α Solar Explorer that provides two-dimensional spectra in the visible light for the full solar disk with a seeing-free condition. The flare shows a prominent enhancement of ∼40% in the photospheric Fe i line at 6569.2 Å, and the nearby continuum also exhibits a maximum enhancement of ∼40%. For the continuum near the Fe i line at 6173 Å from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory, it is enhanced up to ∼20%. At the white-light kernels, the Fe i line at 6569.2 Å has a symmetric Gaussian profile that is still in absorption and the H α line at 6562.8 Å displays a very broad emission profile with a central reversal plus a red or blue asymmetry. The white-light kernels are cospatial with the microwave footpoint sources observed by the Expanded Owens Valley Solar Array and the time profile of the white-light emission matches that of the hard X-ray emission above 30 keV from the Gamma-ray Burst Monitor (GBM) on Fermi. These facts indicate that the white-light emission is qualitatively related to a nonthermal electron beam. We also perform a radiative hydrodynamic simulation with the electron-beam parameters constrained by the hard X-ray observations from Fermi/GBM. The result reveals that the white-light enhancement cannot be well explained by a pure electron-beam heating together with its induced radiative backwarming but may need additional heating sources such as Alfvén waves.

IntroductionReal-time evaluations of the severity of depressive symptoms are of great significance for the diagnosis and treatment of patients with major depressive disorder (MDD). In clinical practice, the evaluation approaches are mainly based on psychological scales and doctor-patient interviews, which are time-consuming and labor-intensive. Also, the accuracy of results mainly depends on the subjective judgment of the clinician. With the development of artificial intelligence (AI) technology, more and more machine learning methods are used to diagnose depression by appearance characteristics. Most of the previous research focused on the study of single-modal data; however, in recent years, many studies have shown that multi-modal data has better prediction performance than single-modal data. This study aimed to develop a measurement of depression severity from expression and action features and to assess its validity among the patients with MDD.MethodsWe proposed a multi-modal deep convolutional neural network (CNN) to evaluate the severity of depressive symptoms in real-time, which was based on the detection of patients’ facial expression and body movement from videos captured by ordinary cameras. We established behavioral depression degree (BDD) metrics, which combines expression entropy and action entropy to measure the depression severity of MDD patients.ResultsWe found that the information extracted from different modes, when integrated in appropriate proportions, can significantly improve the accuracy of the evaluation, which has not been reported in previous studies. This method presented an over 74% Pearson similarity between BDD and self-rating depression scale (SDS), self-rating anxiety scale (SAS), and Hamilton depression scale (HAMD). In addition, we tracked and evaluated the changes of BDD in patients at different stages of a course of treatment and the results obtained were in agreement with the evaluation from the scales.DiscussionThe BDD can effectively measure the current state of patients’ depression and its changing trend according to the patient’s expression and action features. Our model may provide an automatic auxiliary tool for the diagnosis and treatment of MDD.

BackgroundAnti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data.MethodsThis systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity.ResultsWe included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%).ConclusionsIntracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei, and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases.

Abstract Background Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM. Case presentation We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years. Conclusion TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis.

Colitis-associated cancer (CAC) is a subtype of inflammatory bowel disease (IBD)-associated colorectal cancer. Huoxiang Zhengqi (HXZQ) is a classical Chinese herbal medicine and has been used to treat intestinal disorders, however, anti-CAC effects and underlying mechanisms of HXZQ have not been reported. An azoxymethane/dextran sulfate sodium-induced CAC mice model was used to investigate the anti-CAC effect of HXZQ. HXZQ significantly reduced colonic inflammation, suppressed the size and number of tumors, and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-1α, IL-1β, IL-6, IL-17A, IL-21, IL-23, granulocyte macrophage-colony stimulating factor, and tumor necrosis factor-α) and oxidative stress markers (reactive oxygen species and malondialdehyde), and increased the levels of anti-inflammatory cytokines (IL-10 and IL-27) in CAC mice. Intestinal microbiota and serum metabolomics analyses indicated that HXZQ altered the gut microbial composition and the abundance of 29 serum metabolites in CAC mice. Additionally, HXZQ activated the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) signaling pathway and increased the levels of antioxidants such as catalase (CAT), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductases-1 (NQO-1), and superoxide dismutase-1 (SOD-1). HXZQ inhibited the activation of the nuclear factor kappa-B (NF-κB) signaling pathway and decreased the expression of NLR family pyrin domain containing 3 (NLRP3) by inhibiting the phosphorylation of inhibitor of nuclear factor kappa-B (IκB), inhibitor of nuclear factor kappa-B kinase (IKK), and NF-κB. In conclusion, HXZQ alleviated CAC in mice by modulating the intestinal microbiota and metabolism, activating Nrf2-mediated antioxidant response, and inhibiting NF-κB-mediated NLRP3 inflammasome activation against inflammation. The present data provide a reference for the use of HXZQ as a therapeutic or combination agent for clinical CAC treatment.

Coxsackievirus B3 (CVB3) is a positive single-strand RNA virus causing myocarditis, pancreatitis and meningitis. During CVB3 infection, various host cellular components, including proteins and non-coding RNAs, interact with the virus and affect viral infection. Poly(rC) binding protein 1 (PCBP1) is a multifunctional RNA binding protein regulating transcription, translation and mRNA stability of a variety of genes. In this study, we observed a significant reduction of PCBP1 protein during CVB3 infection. By bioinformatic prediction and luciferase-assay verification, we confirmed that the expression of PCBP1 was directly inhibited by miR-21, a microRNA upregulated during CVB3 infection. Furthermore, we found that overexpression of PCBP1 promoted CVB3 infection and knocking down of PCBP1 inhibited it. In the subsequent mechanism study, our results revealed that PCBP1 blocked the translation of p62/SQSTM1 (sequestosome 1), an autophagy-receptor protein suppressing CVB3 replication, by interacting with the cis-element in the 5′ untranslational region (5′ UTR) of p62/SQSTM1. In summary, our studies have identified PCBP1 as a beneficial factor for CVB3 infection. These findings may deepen the understanding of host-virus interactions and provide a potential target for intervention of CVB3 infection.

Fatty liver disease (FLD) is a clinical and pathological syndrome characterized by excessive fat deposition and even steatosis in hepatocytes. It has been proven that liver inflammation induced by fat and its derivatives are involved in the pathogenesis of FLD, while the precise mechanism still remains poorly understood. Pyroptosis is programmed inflammatory cell death driving cell swelling and membrane rupture. Pyroptosis is initiated by the activation of inflammasomes and caspases, which further cleaves and activates various gasdermins, leading to pores forming on the cell membrane and the release of pro-inflammatory factors such as interleukin (IL)-1β and IL-18. Recent studies demonstrate that pyroptosis occurs in hepatocytes, and inhibiting pyroptosis could effectively reduce fat deposition in the liver and could ameliorate inflammation from FLD, attracting our prime focus on the role of pyroptosis in FLD. In this manuscript, we reviewed the current understanding of pyroptosis in FLD development, aiming to provide new insights and potential research targets for the clinical diagnosis and intervention of FLD.

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE−/−) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.

Abstract Background In recent years, talaromycosis is reportedly on the rise in human immunodeficiency virus (HIV)-uninfected patients. However, the misdiagnosis and mistreatment of talaromycosis is more likely in HIV-uninfected patients than in HIV-infected patients because talaromycosis can be easily mistaken for tuberculosis or any other opportunistic infection. Therefore, we used metagenomic next-generation sequencing (mNGS), a novel gene detection method, for the diagnosis of talaromycosis in HIV-uninfected patients. Case presentation We report five cases diagnosed as talaromycosis by mNGS in HIV-uninfected patients, which were further confirmed by tissue culture. There were 3 male and 2 female patients. Two patients had a history of rat contact. The misdiagnosis duration ranged from 88 to 245 days. While the results of tissue culture changed from repeated negative to positive, the mNGS result for Talaromyces marneffei was positive earlier in 4 patients. The reads of Talaromyces marneffei in mNGS ranged from 5 to 414. After antifungal therapy, one of the outcomes was death due to the longest duration of misdiagnosis, and the other outcomes were clinical improvement. Conclusions mNGS is perhaps a rapid and effective diagnosis approach for the early confirmation of talaromycosis. Antifungal therapy is recommended once Talaromyces marneffei was revealed by mNGS. mNGS might reduce misdiagnosis duration and improve prognosis. Through these findings, we hope to provide some reference for talaromycosis in HIV-uninfected patients diagnosed early with the help of mNGS.

Abstract To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4+T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4+T cells (P

Abstract Background Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. Methods Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. Results Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. Conclusion T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

Alzheimer’s disease (AD) is a disease characterized by insidious and progressive neurodegeneration, with clinical syndromes of memory and visuospatial skills damage. The pathogenic mechanism of AD is complex in which neural inflammation and neuron death play important roles. Pyroptosis, an inflammatory programmed cell death, has been reported to be involved in neuron death. Pyroptosis is executed by the protein family of gasdermins which punch pores on plasma membrane when activated by the upstream signals including the activation of NLRP3 and caspases, and subsequently triggers the inflammatory cascades featured by the release of interleukin (IL) -1β and IL-18. Herein, we summarized the current research on the roles of neuron pyroptosis in AD, aiming to provide a comprehensive view of the molecular mechanisms underlying AD pathogenesis and potential therapeutic targets for AD.

Abstract The frequent emergence of coronavirus (CoV) epidemics has seriously threatened public health and stock farming. The major hosts for CoVs are birds and mammals. Although most CoVs inhabit their specific natural hosts, some may occasionally cross the host barrier to infect livestock and even people, causing a variety of diseases. Since the beginning of the new century, increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics, including the recent COVID-19 pandemic. CoVs belong to the Coronaviridae family of the Nidovirales order. Recently, advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature. Here, we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range, genetic variation, genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses. This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses, including epidemic CoVs, which will benefit virological research and viral disease control.

Helicobacter pylori is a major cause of gastric diseases, but the standard therapy is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Here, the authors develop a pH-responsive graphitic nanozyme that is active under low pH gastric conditions, but inactive in intestines, for selective treatment of H. pylori infections.

This study investigated the effect of edible coating (EC), modified atmosphere packaging (MAP), and edible coating + modified atmosphere packaging (EC + MAP) treatments on the quality of fresh-cut pineapples during storage at 4 °C. The quality differences were analyzed by measuring the quality, physiological indicators, and total microbial counts. After 8 d of storage, the brightness (L*) values of the EC + MAP and control samples were 72.76 and 60.83, respectively. The water loss and respiratory rate of the EC + MAP were significantly inhibited from 0% and 29.33 mg CO2 kg−1 h−1 to 4.13% and 43.84 mg CO2 kg−1 h−1, respectively. Furthermore, the fresh-cut pineapples treated with EC + MAP presented a good appearance, with lower total soluble solids (TSS) and relative conductivity and higher titratable acid (TA), ascorbic acid (AA), total phenol content, and firmness compared to the other treatment groups. At the end of storage, the EC + MAP samples exhibited the lowest polyphenol oxidase (PPO) activity, peroxidase (POD) activity, and malondialdehyde (MDA) content at 28.53 U, 60.37 U, and 1.47 nmol·g−1, respectively. Furthermore, the efficiency of EC + MAP treatment exceeded that of EC or MAP alone, preventing key problems involving the surface browning and microbiological safety of the fresh-cut pineapples. The results showed that EC + MAP treatment was more successful in maintaining the storage quality and extending the shelf life of fresh-cut pineapples.