In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of ...adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.
Background
Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL‐33 is elevated and promotes immune cell activation, leading to the development ...of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL‐33‐activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection‐triggered pathophysiology.
Methods
The role of IL‐33/ILC2 axis in RSV‐induced AHR inflammation and eosinophilia were evaluated in the IL‐33‐deficient and YetCre‐13 Rosa‐DTA mice. Myeloid‐specific, IL‐33‐deficient or ST2‐deficient mice were employed to examine the role of IL‐33 and ST2 signaling in myeloid cells.
Results
We found that IL‐33‐activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2‐derived IL‐13 was sufficient for RSV‐driven AHR, since reconstitution of wild‐type ILC2 rescued RSV‐driven AHR in IL‐13‐deficient mice. Meanwhile, myeloid cell‐derived IL‐33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL‐33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL‐33 signaling.
Conclusions
This study highlights the importance of IL‐33‐activated ILC2s in mediating RSV‐triggered AHR and eosinophilia. In addition, IL‐33 signaling in myeloid cells is crucial for airway inflammation.
Respiratory syncytial virus induces ILC2 to produce IL‐5 and IL‐13 through IL‐33, which is crucial for the development of airway hyperreactivity and airway inflammation. Myeloid cell‐derived IL‐33 and suppression of tumorigenicity 2‐positive myeloid cells contribute to cytokine production and cellular inflammation in airway. Both ILC2 and myeloid cell IL‐33 signaling contribute to local and peripheral eosinophilia.
Several randomized controlled trials and real‐world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV‐r) and molnupiravir (MOV) in at‐risk patients with COVID‐19; ...however, the effectiveness of antisevere acute respiratory syndrome‐coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV‐r, in older patients (≥65 years) infected with severe acute respiratory syndrome‐coronavirus 2. Nonhospitalized older patients with COVID‐19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV‐r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all‐cause hospitalization or death during the 30‐day follow‐up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all‐cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27–0.36) during the follow‐up period. For the secondary outcome, the antiviral group had a significantly lower risk of all‐cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28–0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10–0.30) than the control group. Moreover, the reduced risk of all‐cause hospitalization or death remained consistent in patients receiving NMV‐r (HR, 0.279; 95% CI, 0.24–0.33) and MOV (HR, 0.279; 95% CI, 0.21–0.38). Our results revealed that NMV‐r and MOV decreased the all‐cause hospitalization and death rates among older patients with COVID‐19, supporting the use of antivirals in this vulnerable population.
The efficacy of molnupiravir in treating patients with coronavirus disease 2019 (COVID‐19) has been inconsistent across randomized controlled trials (RCTs). Thus, this meta‐analysis was conducted to ...clarify the literature. A literature search of electronic databases—PubMed, Embase, and Cochrane Library—was performed to identify relevant articles published up to December 31, 2022. Only RCTs that investigated the clinical efficacy and safety of molnupiravir for patients with COVID‐19 were included. The primary outcome was all‐cause mortality at 28–30 days. This pooled analysis of nine RCTs did not reveal a significant difference in all‐cause mortality between molnupiravir and control groups (risk ratio RR, 0.43; 95% confidence interval CI, 0.10–1.77) for overall patients. However, the risks of mortality and hospitalization were lower in the molnupiravir group than in the control group (mortality: RR, 0.28; 95% CI, 0.10–0.79; hospitalization: RR, 0.67; 95% CI, 0.45–0.99) among nonhospitalized patients. In addition, molnupiravir use was associated with a borderline higher virological eradication rate relative to the control (RR, 1.05; 95% CI, 1.00–1.11). Finally, no significant difference in adverse event risk was discovered between the groups (RR, 0.98; 95% CI, 0.89–1.08). The findings reveal the clinical benefits of molnupiravir for nonhospitalized patients with COVID‐19. However, molnupiravir may not improve the clinical outcomes of hospitalized patients. These findings support the recommended use of molnupiravir for treating nonhospitalized patients with COVID‐19 but not for hospitalized patients.
This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia ...(sCAP).
A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality.
A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio RR, 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I
= 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53).
In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.
Short‐wave infrared (SWIR) quantum dot (QD)‐converted photodetectors are one of the promising devices used in artificial intelligence and automatic navigation systems. However, compared to ...semi‐conductor‐type photodetectors, they suffer from poor chemical stability and weak electronic conductivity. In this study, a PbS QD and conductive metal–organic framework (MOF) hybrid composite is designed with SWIR detection capability. The Fourier‐transform infrared spectroscopy confirms the surface modification of PbS QDs with MOF. X‐ray absorption near‐edge structures spectra reveal the chemical bonding between MOF and PbS QDs. Furthermore, 2D grazing‐incidence small‐ and wide‐angle X‐ray scattering is utilized to unveil the particle stacking and the preferred orientation of the PbS@MOF thin film. By integrating the PbS@MOF thin film directly on top of the graphene field effect transistor (FET) device, the chemical stability and photoelectric properties of graphene FET are enhanced, and these are investigated using a focus ion beam with a high‐resolution transmission electron microscope. This study offers a strategy to simultaneously improve the chemical stability and the photoelectronic properties of the nanomaterials as well as contribute to the advancement of a QD‐converted SWIR photodetector.
A PbS quantum dot (QD) and conductive metal–organic framework (MOF) hybrid composite is designed with short‐wave infrared (SWIR) detection capability with the chemical bonding between MOF and PbS QDs. By integrating the PbS@MOF thin film directly on top of the graphene field effect transistor device, a highly stable and efficient charge transport SWIR photodetector can be achieved.
The retrospective cohort was conducted to assess the effect of nirmatrelvir‐ritonavir (NMV‐r) on the long‐term risk of neuropsychiatric sequela following COVID‐19. TriNetX research network was used ...to identify nonhospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 infection or were diagnosed with COVID‐19 between March 1, 2020 and July 1, 2022. Further propensity score matching method was used to create two matched cohorts with and without receiving NMV‐r. The primary outcome was the incidence of neuropsychiatric sequela within a 90‐day to 1‐year period following a diagnosis of COVID‐19. After screening 119 494 527 electronic health records, two matched cohorts of each 27 194 patients were identified. During the follow‐up period, the NMV‐r group demonstrated a reduced risk of any neuropsychiatric sequelae compared to the control group (odds ratio OR, 0.634; 95% confidence interval CI, 0.604−0.667). In comparison with the control group, the patient treated with NMV‐r exhibited a markedly diminished risk of developing neurocognitive sequela (OR, 0.377; 95% CI, 0.325−0.439) and psychiatric sequela (OR, 0.629; 95% CI, 0.593−0.666). In addition, patients treated with NMV‐r had a significantly reduced risk of developing dementia (OR, 0.365; 95% CI, 0.255−0.522), depression (OR, 0.555; 95% CI, 0.503−0.612), insomnia (OR, 0.582; 95% CI, 0.508−0.668) and anxiety disorder (OR, 0.645 95% CI, 0.600−0.692). Moreover, the beneficial effect of NMV‐r on the neuropsychiatric sequelae was observed across further subgroup analyses. Among nonhospitalized COVID‐19 patients, who at risk of disease progression, the use of NMV‐r is associated with a reduction in the long‐term risk of neuropsychiatric sequela, including dementia, depression, insomnia and anxiety disorder. It may be necessary to re‐evaluate the use of NMV‐r, as a preventive measure to reduce the risk of severe acute disease and post‐acute adverse mental health outcomes.
The effect of nirmatrelvir plus ritonavir (NMV‐r) on post‐acute COVID‐19 sequelae beyond 3 months of SARS‐CoV‐2 infection remains unknown. This retrospective cohort study utilized data from the ...TriNetX Research Network. We identified nonhospitalized adult patients with COVID‐19 receiving a diagnosis between January 1 and July 31, 2022. Propensity score matching (PSM) was used to create two matched cohorts: NMV‐r and non‐NMV‐r groups, respectively. We measured the primary outcomes using a composite of all‐cause emergency room (ER) visits or hospitalization and a composite of post‐COVID‐19 symptoms according to the WHO Delphi consensus, which also stated that post COVID‐19 condition occurs usually 3 months from the onset of COVID‐19, during the follow‐up period between 90 days after the index diagnosis of COVID‐19 and the end of follow‐up (180 days). Initially, we identified 12 247 patients that received NMV‐r within 5 days of diagnosis and 465 135 that did not. After PSM, 12 245 patients remained in each group. During the follow‐up period, patients treated with NMV‐r had a lower risk of all‐cause hospitalization and ER visits compared with untreated patients (659 vs. 955; odds ratio OR, 0.672; 95% confidence interval CI, 0.607–0.745; p < 0.0001). However, the overall risk of post‐acute COVID‐19 symptoms did not significantly differ between the two groups (2265 vs. 2187; OR, 1.043; 95% CI, 0.978–1.114; p = 0.2021). The reduced risk of all‐cause ER visits or hospitalization in the NMV‐r group and the similarities in the risk of post‐acute COVID‐19 symptoms between the two groups were consistent in the subgroups stratified by sex, age, and vaccination status. Early NMV‐r treatment of nonhospitalized patients with COVID‐19 was associated with reduced risk of hospitalization and ER visits during the period of 90–180 days after diagnosis compared with no NMV‐r treatment; however, post‐acute COVID‐19 symptoms and mortality risk did not differ significantly between the groups.
In recent years, the low‐cost diamond‐wire (DW) slicing has been widely used for single‐crystalline silicon (sc‐Si) wafers, and this makes sc‐Si solar cells very attractive to the market. On the ...contrary, the adoption of DW slicing for multicrystalline (mc‐Si) wafers is troublesome because of poor texturing quality in the existing production lines using acid solutions. We have developed a vapor texture etching (VTE) process with the combination of both acid and reacted vapors for DW sliced mc‐Si wafers. The etching process was rather simple and low cost. More importantly, the acid usage was low and recyclable, so that the acid emission was low as well. Its scale‐up was easy and straightforward. In this lab‐scale reactor, more than 50 full‐size wafers could be processed each time. The etched wafers had uniform appearance and low reflectivity, around 10%. After the nanostructure pores were enlarged by post treatments to minimize surface recombination, the full‐size mc‐Si solar cell fabricated by Solartech could achieve an efficiency of 19.7% using the Passivated Emitter and Rear Contact (PERC) structure, which was comparable with the average production efficiency.
We developed a vapor texture etching (VTE) process that was rather simple and low cost. Its scale‐up was easy and straightforward. In this lab‐scale reactor, more than 50 full‐size wafers could be processed each time. The etched wafers had uniform appearance and low reflectivity, around 10%. After the nanostructure pores were enlarged by post treatments to minimize surface recombination, the mc‐Si solar cell could achieve an efficiency of 19.5% using the Passivated Emitter and Rear Contact (PERC) structure.
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