Alzheimer's disease with depressive symptoms: Clinical effect of intermittent theta burst stimulation repetitive transcranial magnetic stimulation.

BACKGROUND: Alzheimer's disease (AD), characterized by the ongoing deterioration of neural function, often presents alongside depressive features and greatly affects the quality of life of individuals living with the condition. Although several treatment methods exist, their efficacy is limited. In recent years, repetitive transcranial magnetic stimulation (rTMS) utilizing the theta burst stimulation (TBS) mode, specifically the intermittent TBS (iTBS), has demonstrated promising therapeutic potential in the management of neuropsychiatric disorders. AIM: To examine the therapeutic efficacy of iTBS mode of rTMS for treating depressive symptoms in patients with AD. METHODS: This retrospective study enrolled 105 individuals diagnosed with AD with depressive symptoms at Huzhou Third Municipal Hospital, affiliated with Huzhou University, between January 2020 and December 2023. Participants received standard pharmacological interventions and were categorized into control (n = 53) and observation (n = 52) groups based on treatment protocols. The observation group received iTBS mode of rTMS, while the control group received pseudo-stimulation. A comparative analysis evaluated psychological well-being, adverse events, and therapeutic at initiation of hospitalization (T0) and 15 days post-treatment (T1). RESULTS: At T1, both groups exhibited a marked reduction in self-rating depression scale and Hamilton depression scale scores compared to T0. Furthermore, the observation group showed a more pronounced decrease than the control group. By T1, the Mini-mental state examination scores for both groups had increased markedly from their initial T0 assessments. Importantly, the increase was particularly more substantial in the observation group than in the control group. Fourteen patients in the control group had ineffective treatment effects, while five patients in the observation group experienced the same. Additionally, the observation group experienced a substantially reduced incidence of ineffective treatment as compared to the control group (both P < 0.05); there were no recorded serious adverse events in either group. CONCLUSION: The iTBS model of rTMS effectively treated AD with depression, improving depressive symptoms and cognitive function in patients without serious adverse reactions, warranting clinical consideration.

Prodrug-based nanomedicines for rheumatoid arthritis.

Most antirheumatic drugs with high toxicity exhibit a narrow therapeutic window due to their nonspecific distribution in the body, leading to undesirable side effects and reduced patient compliance. To in response to these challenges, prodrug-based nanoparticulate drug delivery systems (PNDDS), which combines prodrug strategy and nanotechnology into a single system, resulting their many advantages, including stability for prodrug structure, the higher drug loading capacity of the system, improving the target activity and bioavailability, and reducing their untoward effects. PNDDS have gained attention as a method for relieving arthralgia syndrome of rheumatoid arthritis in recent years. This article systematically reviews prodrug-based nanocarriers for rheumatism treatment, including Nano systems based on prodrug-encapsulated nanomedicines and conjugate-based nanomedicines. It provides a new direction for the clinical treatment of rheumatoid arthritis.

Chronic exposure to aflatoxin B1 increases hippocampal microglial pyroptosis and vulnerability to stress in mice.

BACKGROUND: Chronic aflatoxin B1 (AFB1) exposure may increase the risk of multiple neuropsychiatric disorders. Stress is considered one of the main contributors to major depressive disorder. Whether and how chronic AFB1 exposure affects vulnerability to stress is unclear. METHODS: Mice were exposed for three weeks to AFB1 (100 µg/kg/d) and/or chronic mild stress (CMS). The vulnerability behaviors in response to stress were assessed in the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST). Microglial pyroptosis was investigated using immunofluorescence, enzyme-linked immunosorbent assays, and western blot assay in the hippocampus of mice. Hippocampal neurogenesis and the effects of AFB1-treated microglia on proliferation and differentiation of neural stem/precursor cells (NSPCs) were assessed via immunofluorescence in the hippocampus of mice. RESULTS: Mice exposed to CMS in the presence of AFB1 exhibited markedly greater vulnerability to stress than mice treated with CMS or AFB1 alone, as indicated by reduced sucrose preference and longer immobility time in the forced swimming test. Chronic aflatoxin B1 exposure resulted in changes in the microglial morphology and increase in TUNEL+ microglia and GSDMD+ microglia in the hippocampal dentate gyrus. When mice were exposed to both CMS and AFB1, pyroptosis-related molecules (such as NLRP3, caspase-1, GSDMD-N, and interleukin-1ß) were significantly upregulated in the hippocampus. These molecules were also significantly enhanced by AFB1 in primary microglial cultures. AFB1-treated mice showed decrease in the numbers of BrdU+, BrdU-DCX+, and BrdU-NeuN+ cells in the hippocampal dentate gyrus, as well as the percentages of BrdU+ cells that were NeuN+ in the presence or absence of CMS when compared with vehicle-treated mice. The combination of AFB1 and CMS exacerbated these effects to an even greater extent. The number of DCX+ cells correlated negatively with the percentage of ameboid microglia, TUNEL+ microglia and GSDMD+ microglia in the hippocampal dentate gyrus. AFB1-treated microglia suppressed the proliferation and neuronal differentiation of NSPCs in vitro. CONCLUSION: Chronic AFB1 exposure induces microglial pyroptosis, promoting an adverse neurogenic microenvironment that impairs hippocampal neurogenesis, which may render mice more vulnerable to stress.

Gastrodin programs an Arg-1+ microglial phenotype in hippocampus to ameliorate depression- and anxiety-like behaviors via the Nrf2 pathway in mice.

BACKGROUND: Regulating the microglial phenotype is an attractive strategy for treating diseases of the central nervous system such as depression and anxiety. Gastrodin can quickly cross the blood-brain barrier and mitigate microglia-mediated inflammation, which widely used to treat a variety of central nervous system diseases associated with microglial dysfunction. However, the molecular mechanism by which gastrodin regulates the functional phenotype of microglia remains unclear. PURPOSE: Since the transcription factor "nuclear factor erythroid 2-related factor 2″ (Nrf2) is associated with the anti-inflammatory effects of gastrodin, we hypothesized that gastrodin induces Nrf2 expression in microglia and thereby programs an anti-inflammatory phenotype. STUDY DESIGN: Male C57BL/6 mice, treated or not with gastrodin, were given lipopolysaccharide (LPS) at 0.25 mg/kg/d for 10 days to induce chronic neuroinflammation. The effects of gastrodin on microglial phenotypes, neuroinflammation and depression- and anxiety-like behaviors were evaluated. In another experiment, animals were treated with Nrf2 inhibitor ML385 throughout the 13-day gastrodin intervention period. METHODS: The effects of gastrodin on depression- and anxiety-like behaviors were evaluated through the sucrose preference test, forced swimming test, open field test and elevated plus-maze test; as well as its effects on morphology and molecular and functional phenotypes of hippocampal microglia through immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assays. RESULTS: Chronic exposure to LPS caused hippocampal microglia to secrete inflammatory cytokines, their somata to enlarge, and their dendrites to lose branches. These changes were associated with depression- and anxiety-like behaviors. Gastrodin blocked these LPS-induced alterations and promoted an Arg-1+ microglial phenotype that protected neurons from injury. The effects of gastrodin were associated with Nrf2 activation, whereas blockade of Nrf2 antagonized gastrodin. CONCLUSION: These results suggest that gastrodin acts via Nrf2 to promote an Arg-1+ microglial phenotype, which buffers the harmful effects of LPS-induced neuroinflammation. Gastrodin may be a promising drug against central nervous system diseases that involve microglial dysfunction.

Soil Microbial Communities Affect the Growth and Secondary Metabolite Accumulation in Bletilla striata (Thunb.) Rchb. f.

Bletilla striata (Thunb.) Rchb.f. is a perennial herb belonging to the Orchidaceae family. Its tubers are used in traditional Chinese medicine to treat gastric ulcers, inflammation, silicosis tuberculosis, and pneumogastric hemorrhage. It has been reported that different soil types can affect the growth of B. striata and the accumulation of secondary metabolites in its tubers, but the biological mechanisms underlying these effects remain unclear. In this study, we compared agronomic traits and the accumulation of secondary metabolites (extractum, polysaccharide, total phenol, militarine) in B. striata grown in sandy loam or sandy clay soil. In addition, we compared physicochemical properties and microbial communities between the two soil types. In pot experiments, we tested how irradiating soil or transplanting microbiota from clay or loam into soil affected B. striata growth and accumulation of secondary metabolites. The results showed that sandy loam and sandy clay soils differed significantly in their physicochemical properties as well as in the structure and composition of their microbial communities. Sandy loam soil had higher pH, SOM, SOC, T-Ca, T-N, T-Mg, T-Mn, T-Zn, A-Ca, A-Mn, and A-Cu than sandy clay soil, but significantly lower T-P, T-K, T-Fe, and A-P content. Sandy loam soil showed 7.32% less bacterial diversity based on the Shannon index, 19.59% less based on the Ace index, and 24.55% less based on the Chao index. The first two components of the PCoA explained 74.43% of the variation in the bacterial community (PC1 = 64.92%, PC2 = 9.51%). Similarly, the first two components of the PCoA explained 58.48% of the variation in the fungal community (PC1 = 43.67%, PC2 = 14.81%). The microbiome associated with sandy clay soil can promote the accumulation of militarine in B. striata tubers, but it inhibits the growth of B. striata. The accumulation of secondary metabolites such as militarine in B. striata was significantly higher in sandy clay than in sandy loam soil. Conversely, B. striata grew better in sandy loam soil. The microbiome associated with sandy loam soil can promote the growth of B. striata, but it reduces the accumulation of militarine in B. striata tubers. Pot experiment results further confirmed that the accumulation of secondary metabolites such as militarine was higher in soil transplanted with loam microbiota than in soil transplanted with clay microbiota. These results may help guide efforts to improve B. striata yield and its accumulation of specific secondary metabolites.

The effects of a multi-disciplinary team on sleep quality assessment in mild-to-moderate Alzheimer's disease patients with sleep disorders.

BACKGROUND AND AIMS: Sleep disturbances are a severe problem among patients with Alzheimer's disease (AD). By evaluating sleep quality in mild-to-moderate AD patients, this study aimed to assess the effects of multi-disciplinary team (MDT) in reducing the incidence of adverse reactions of AD patients. The reduction in the incidence of adverse reactions to predict multi-disciplinary team (MDT) treatment effects. METHODS AND RESULTS: This study included 60 mild-to-moderate AD patients with sleep problems when hospitalized in Huzhou Third Municipal Hospital. The patients were randomly distributed into two groups, routine and MDT treatments. The cognitive functions, sleep conditions, and psycho-behavioral symptoms were compared between both the groups. Cognitive function declined significantly between pretherapy and follow-up in the routine treatment group (MMSE: t = -7.961, P < 0.001; MoCA: t = -4.672, P < 0.001). There was a significant decline in drowsiness in the MDT group compared to that in the routine treatment group (χ2 = 4.320, P = 0.038). Sleep quality improved significantly during the follow-up in the MDT treatment group (t = 6.098, P < 0.001). The results of the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) among family caregivers (FCGs) demonstrated that MDT treatment could alleviate caregivers' depression (t = -2.867, P = 0.042), and routine treatment can worsen their anxiety (t = 3.258, P = 0.003). CONCLUSION: The MDT treatment method as an effective and meaningful therapy can help mitigate the suffering of patients with AD and FCGs.

Method to measure the position offset of multiple light spots in a distributed aperture laser angle measurement system.

In this paper, an accurate measurement method of multiple spots' position offsets on a four-quadrant detector is proposed for a distributed aperture laser angle measurement system (DALAMS). The theoretical model is put forward, as well as the corresponding calculation method. This method includes two steps. First, as the initial estimation, integral approximation is applied to fit the distributed spots' offset function; second, the Boltzmann function is employed to compensate for the estimation error to improve detection accuracy. The simulation results attest to the correctness and effectiveness of the proposed method, and tolerance synthesis analysis of DALAMS is conducted to determine the maximum uncertainties of manufacturing and installation. The maximum angle error is less than 0.08° in the prototype distributed measurement system, which shows the stability and robustness for prospective applications.

Large field distributed aperture laser semiactive angle measurement system design with imaging fiber bundles.

A type of laser semiactive angle measurement system is designed for target detecting and tracking. Only one detector is used to detect target location from four distributed aperture optical systems through a 4×1 imaging fiber bundle. A telecentric optical system in image space is designed to increase the efficiency of imaging fiber bundles. According to the working principle of a four-quadrant (4Q) detector, fiber diamond alignment is adopted between an optical system and a 4Q detector. The structure of the laser semiactive angle measurement system is, we believe, novel. Tolerance analysis is carried out to determine tolerance limits of manufacture and installation errors of the optical system. The performance of the proposed method is identified by computer simulations and experiments. It is demonstrated that the linear region of the system is ±12°, with measurement error of better than 0.2°. In general, this new system can be used with large field of view and high accuracy, providing an efficient, stable, and fast method for angle measurement in practical situations.

Design of compact LED free-form optical system for aeronautical illumination.

A type of runway centerline light is designed for the application of light-emitting diode (LED) aeronautical illumination. A total internal reflection collimating lens and an integrated prism are designed, respectively, to meet the intensity distribution of International Convention on Civil Aviation (ICAO) regulations. The principle of geometric optics is adopted to construct the free-form surfaces of a collimating lens, which is simple. Different variations are used in the process of free-form surface calculation. An integrated prism with a diffuser is used for uniformly diffusing rays and then decreasing the central maximum intensity to avoid glare. The structure of the optical system is compact. Computer simulation results show that an optical efficiency of 79.2% is achieved for a 1 mm×1 mm LED source. Tolerance analysis is carried out to determine tolerance limits of manufacture and installation errors. To verify the optical performance of the proposed runway centerline light, the practical illumination distribution is measured by using Cree XP-E2 LED, which can comply with ICAO regulations.

The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation.

A facile method via 1,3-dipolar cycloaddition of substituted benzylidene-2-phenyloxazolone under mild conditions with azomethine ylides, which were generated in situ by a decarboxylative route from a common set of diverse isatins and amino acid derivatives was developed for a 15-membered library of regio- and stereoselective oxazolones-grafted spirooxindole-pyrrolidine, pyrrolizidines and pyrrolothiazoles. After screening their cytotoxic activities against a spectrum of cell-lines, compound 4h was identified as potent antitumor agent and inducing apoptosis. The present study has provided an effective entry to rapidly construct a chemical library of oxazolones-grafted spirooxindoles and developed a good lead compound for subsequent optimization.