sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-ß via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

Saponin and Ribosome-Inactivating Protein Synergistically Trigger Lysosome-Dependent Apoptosis by Inhibiting Lysophagy: Potential to Become a New Antitumor Strategy.

The susceptibility of lysosomal membranes in tumor cells to cationic amphiphilic drugs (CADs) enables CADs to induce lysosomal membrane permeabilization (LMP) and trigger lysosome-dependent cell death (LDCD), suggesting a potential antitumor therapeutic approach. However, the existence of intrinsic lysosomal damage response mechanisms limits the display of the pharmacological activity of CADs. In this study, we report that low concentrations of QS-21, a saponin with cationic amphiphilicity extracted from Quillaja Saponaria tree, can induce LMP but has nontoxicity to tumor cells. QS-21 and MAP30, a type I ribosome-inactivating protein, synergistically induce apoptosis in tumor cells at low concentrations of both. Mechanistically, QS-21-induced LMP helps MAP30 escape from endosomes or lysosomes and subsequently enter the endoplasmic reticulum, where MAP30 downregulates the expression of autophagy-associated LC3 proteins, thereby inhibiting lysophagy. The inhibition of lysophagy results in the impaired clearance of damaged lysosomes, leading to the leakage of massive lysosomal contents such as cathepsins into the cytoplasm, ultimately triggering LDCD. In summary, our study showed that coadministration of QS-21 and MAP30 amplified the lysosomal disruption and can be a new synergistic LDCD-based antitumor therapy.

Azobenzene-Based Linker Strategy for Selective Activation of Antibody-Drug Conjugates.

Existing antibody-drug conjugate (ADC) linkers, whether cleavable or non-cleavable, are designed to release highly toxic payloads or payload derivatives upon internalisation of the ADCs into cells. However, clinical studies have shown that only <1 % of the dosed ADCs accumulate in tumour cells. The remaining >99 % of ADCs are nonspecifically distributed in healthy tissue cells, thus inevitably leading to off-target toxicity. Herein, we describe an intelligent tumour-specific linker strategy to address these limitations. A tumour-specific linker is constructed by introducing a hypoxia-activated azobenzene group as a toxicity controller. We show that this azobenzene-based linker is non-cleavable in healthy tissues (O2 >10 %), and the corresponding payload derivative, cysteine-appended azobenzene-linker-monomethyl auristatin E (MMAE), can serve as a safe prodrug to mask the toxicity of MMAE (switched off). Upon exposure to the hypoxic tumour microenvironment (O2<1 %), this linker is cleaved to release MMAE and fully restores the high cytotoxicity of the ADC (switched on). Notably, the azobenzene linker-containing ADC exhibits satisfactory antitumour efficacy in vivo and a larger therapeutic window compared with ADCs containing traditional cleavable or non-cleavable linkers. Thus, our azobenzene-based linker sheds new light on the development of next-generation ADC linkers.

Nutrient supplementation among pregnant women in China: an observational study.

OBJECTIVE: To clarify nutrient supplementation usage and primary source of information among pregnant women in China. DESIGN: This cross-sectional study used information on nutrient supplementation and primary source of information collected via face-to-face interviews. Data on the usage of folic acid, Ca/vitamin D, Fe, vitamins, DHA and other dietary supplements were collected. Primary source of information was categorised as family/relatives, friends/co-workers, the Internet, books/magazines, television/radio, doctors, other people and oneself. SETTING: Maternal and Child Health Hospital in Chengdu, China. PARTICIPANTS: One thousand eighty-one Chinese pregnant women aged ≥20 years with singleton pregnancies. RESULTS: In all three trimesters of pregnancy, usage was highest and most stable for folic acid (81·7 %), followed by vitamins (vitamin A, B-group vitamins, vitamin C and multivitamins; 75·0 %), whereas Ca/vitamin D (51·4 %) and Fe (18·1 %) usage was low, potentially indicating a deficiency risk. All supplementation usage percentages increased with pregnancy duration (P < 0·05). Notably, approximately 10 % of the pregnant women in our study did not use any nutrient supplementation, and this was especially common in early pregnancy. More than 50 % of the women reported getting information on nutrient supplementation from family members, and about 30 % reported getting this information from doctors. CONCLUSIONS: Among pregnant women in China, awareness about nutrient supplementation increases as the pregnancy progresses, but some types of nutrient supplementation (such as Ca/vitamin D and Fe) remain at low levels. It is necessary to pay more attention to the health education of pregnant women in China, and the influence of family members should be emphasised.

Factors associated with burnout among medical laboratory professionals in Ontario, Canada: An exploratory study during the second wave of the COVID-19 pandemic.

OBJECTIVE: The objective of this study was to examine factors associated with burnout among medical laboratory technologists (MLT) in Ontario, Canada during the second wave of coronavirus disease 2019 pandemic. METHODS: We employed a cross-sectional design and used a self-reported questionnaire designed for MLT in Ontario, Canada. RESULTS: There were 441 (47.5% response rate) MLT who were included in the analytic sample. Most of the respondents were women, with a mean age of 43.1 and a standard deviation of 11.7. The prevalence of experiencing burnout was 72.3% for MLT. In the adjusted demographic model, those ≥50 (OR = 0.36, 95% CI: 0.22-0.59) were 0.36 or about one third as likely to experience burnout as those under 50. Similarly, those who held a university degree were less likely to experience burnout compared with high school degree (OR = 0.35, 95% CI: 0.15-0.79). In the adjusted occupational model, high quantitative demands (OR = 2.15, 95% CI: 1.21-3.88), high work pace (OR = 2.21, 95% CI: 1.25-3.98), high job insecurity (OR = 2.56, 95% CI: 1.39-4.82), high work life conflict (OR = 5.08, 95% CI: 2.75-9.64) and high job satisfaction (OR = 0.43, 95% CI: 0.20-0.88), high self-rated health (OR = 0.32, 95% CI: 0.17-0.56) were significant. CONCLUSION: This study provides preliminary evidence regarding the factors associated with burnout in MLT. Additional research is needed to understand their relationship with workers health and well-being and in the delivery of health services.

Glutathione Depletion-Induced Activation of Dimersomes for Potentiating the Ferroptosis and Immunotherapy of "Cold" Tumor.

The abundant glutathione (GSH) in "cold" tumors weakens ferroptosis therapy and the immune response. Inspired by lipids, we fabricated cinnamaldehyde dimers (CDC) into lipid-like materials to form dimersomes capable of depleting GSH and delivering therapeutics to potentiate the ferroptosis and immunotherapy of breast cancer. The dimersomes exhibited superior storage stability for over one year. After reaching the tumor, they quickly underwent breakage in the cytosol owing to the conjugation of hydrophilic GSH on CDC by Michael addition, which not only triggered the drug release and fluorescence switch "ON", but also led to the depletion of intracellular GSH. Ferroptosis was significantly enhanced after combination with sorafenib (SRF) and elicited a robust immune response in vivo by promoting the maturation of dendritic cells and the priming of CD8+ T cells. As a result, the CDC@SRF dimersomes cured breast cancer in all the mice after four doses of administration.

Scalable distributed microwave photonic MIMO radar based on a bidirectional ring network.

A scalable distributed microwave photonic multiple-input-multiple-output (MIMO) radar is proposed based on a bidirectional ring network. The network is constructed with a fiber ring on which a local node and several remote nodes are distributed. In the local node, radar signals are generated over different optical wavelengths based on external modulation. Employing wavelength-division multiplexing, the radar signals are sent to remote nodes through the fiber ring. In different remote nodes, radar signals modulated on corresponding wavelength are utilized for transmitting or photonic de-chirp processing. Benefiting from the bidirectional ring network, the proposed radar is suitable for large-scale distribution. Together with the pluggable remote nodes, the scalability of the radar is enhanced. A proof-of-concept experiment is demonstrated to verify the feasibility of the system. Measurements of two-dimensional position and velocity of targets are realized. The position error and velocity error are better than 8 cm and 0.20 m/s respectively.

Microwave photonic de-chirp receiver for breaking the detection range swath limitation.

A novel microwave photonics-based de-chirp radar receiver which breaks the limitation of the detection range swath is proposed and demonstrated. In the proposed receiver, a multi-channel time-division photonics de-chirp processing is implemented to increase the detection range swath. A linear frequency modulated pulse train is sent to multiple reception channels and temporally delayed in the optical domain to form reference signal replicas, enabling time-division photonics-de-chirp processing with echoes reflected from different distance regions so that the total detection range swath is increased and determined by the number of reference replicas. Hardware-in-the-loop simulation experiments are demonstrated and an inverse synthetic aperture 2D imaging is carried out, showing that the MWP radar with the proposed photonics de-chirp receiver is capable of achieving a detection range swath of 13km which is 20 times larger than that when employing a conventional de-chirp receiver with the same parameters.

Microwave photonic radar with a fiber-distributed antenna array for three-dimensional imaging.

A microwave photonic (MWP) radar with a fiber-distributed antenna array for three-dimensional (3D) imaging is proposed and demonstrated for the first time. Photonic frequency doubling, wavelength-division multiplexing and radio-over-fiber techniques are employed for radar signal generation, replication, and distribution. Based on the delay-dependent beat frequency division, parallel de-chirp processing is completed in the center office (CO), leading to multi-channel 2D ISAR imaging and further 3D reconstruction. The influence of the fiber transmission delay is discussed and the phase noise caused thereby is compensated in 3D imaging algorithm, improving the coherence between channels. An experiment of a Ku-band MWP radar with a transmitter (Tx) and 16 equivalent receivers (Rxs) is conducted and 3D imaging of three trihedral corner reflectors is achieved with a range resolution of 7.3 cm, a cross-rage resolution of 5.6 cm and an elevation resolution of 0.85°. The results verify the capability of MWP radar in high-resolution 3D imaging.

Channelized photonic-assisted deramp receiver with an extended detection distance along the range direction for LFM-CW radars.

A novel photonic-assisted deramp receiver extends detection distance along range direction of linearly-frequency-modulated continuous wave (LFM-CW) radars is proposed. A dual-polarization quadrature phase shift keying (DP-QPSK) modulator is used to modulate an optical frequency-comb (OFC) to generate orthogonally polarized optical signals. Then the orthogonally polarized optical signals are coherently detected with an optical local oscillator (OLO), which is generated by modulating the other OFC with the RF-reference signal on a null-biased Mach-Zehnder modulator (MZM). At the output of each detection unit, beating results can be recovered using a digital signal processing algorithm. By stitching the beating results of several paralleled detection units, the deramp signal corresponded to an extended range distance can be recovered. The proposed technique is experimentally evaluated through both simulated echoes and real echoes of two static trihedral corner reflectors (TCRs) distributed along range direction.

Wide-band RF receiver based on dual-OFC-based photonic channelization and spectrum stitching technique.

A novel wide-band RF receiver based on a dual-OFC-based channelization and spectrum stitching technique is proposed and demonstrated experimentally. In the scheme, a dual-OFC-based channelizer is utilized as the front-end to slice the RF signals into multiple channels. In the back-end, through the channel estimation and spectrum stitching, the received signals can be well reconstructed in the digital domain. A proof-of-concept experiment is performed, in which signals with 3 GHz bandwidths are sliced and reconstructed using the proposed receiver with a normalized mean squared error (NMSE) of 7.9×10-3. The performances of the reconstructed signals on pulse compression are also demonstrated to evaluate the potential of the proposed technique in practical applications.

[Design, synthesis and pharmacological investigation of isoindoline derivatives as 5-HT/NE double reuptake inhibitors].

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.

Herbal Insomnia Medications that Target GABAergic Systems: A Review of the Psychopharmacological Evidence.

Insomnia is a common sleep disorder which is prevalent in women and the elderly. Current insomnia drugs mainly target the γ-aminobutyric acid (GABA) receptor, melatonin receptor, histamine receptor, orexin, and serotonin receptor. GABAA receptor modulators are ordinarily used to manage insomnia, but they are known to affect sleep maintenance, including residual effects, tolerance, and dependence. In an effort to discover new drugs that relieve insomnia symptoms while avoiding side effects, numerous studies focusing on the neurotransmitter GABA and herbal medicines have been conducted. Traditional herbal medicines, such as Piper methysticum and the seed of Zizyphus jujuba Mill var. spinosa, have been widely reported to improve sleep and other mental disorders. These herbal medicines have been applied for many years in folk medicine, and extracts of these medicines have been used to study their pharmacological actions and mechanisms. Although effective and relatively safe, natural plant products have some side effects, such as hepatotoxicity and skin reactions effects of Piper methysticum. In addition, there are insufficient evidences to certify the safety of most traditional herbal medicine. In this review, we provide an overview of the current state of knowledge regarding a variety of natural plant products that are commonly used to treat insomnia to facilitate future studies.

[Evaluation of the sedative and hypnotic effects of H1208].

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

Momentum prediction models of tennis match based on CatBoost regression and random forest algorithms.

As we all know, momentum plays a crucial role in ball game. Based on the 2023 Wimbledon final data, this paper investigated momentum in tennis. Firstly, we initially trained a decision tree regression model on reprocessed data for prediction, and established the CBRF model based on CatBoost regression and random forest regression models to obtain prediction data. Secondly, significant non-zero autocorrelation coefficients were found, confirming the correlation between momentum and success. Thirdly, Based on these key factors, we proposed winning strategies for the players, conducted predictive analyses for six specific time intervals of the game. At last, by implementing these models to women's matches, championships, matches on different surfaces, the results demonstrated that the models have effective generalization ability.

Centrifugal Inertia-Induced Directional Alignment of AgNW Network for Preparing Transparent Electromagnetic Interference Shielding Films with Joule Heating Ability.

Transparent electromagnetic interference (EMI) shielding is highly desired in specific visual scenes, but the challenge remains in balancing their EMI shielding effectiveness (SE) and optical transmittance. Herein, this study proposed a directionally aligned silver nanowire (AgNW) network construction strategy to address the requirement of high EMI SE and satisfactory light transmittance using a rotation spraying technique. The orientation distribution of AgNW is induced by centrifugal inertia force generated by a high-speed rotating roller, which overcomes the issue of high contact resistance in random networks and achieves high conductivity even at low AgNW network density. Thus, the obtained transparent conductive film achieved a high light transmittance of 72.9% combined with a low sheet resistance of 4.5 Ω sq-1 and a desirable EMI SE value of 35.2 dB at X band, 38.9 dB in the K-band, with the highest SE of 43.4 dB at 20.4 GHz. Simultaneously, the excellent conductivity endowed the film with outstanding Joule heating performance and defogging/deicing ability, ensuring the visual transparency of windows when shielding electromagnetic waves. Hence, this research presents a highly effective strategy for constructing an aligned AgNW network, offering a promising solution for enhancing the performance of optical-electronic devices.

FTIR determination of the degree of molar substitution for hydroxypropyl chitosan.

We developed and validated a novel Fourier transform infrared (FTIR) method to determine the degree of molar substitution (MS) for hydroxypropyl chitosan (HPCS) using nuclear magnetic resonance (1H NMR) as a reference, and investigated the factors influencing the MS assay. Through extensive screening of integration methods for candidate bands in the FTIR spectrum of HPCS using 20 HPCS samples with degrees of acetylation (DA) ranging from 0.003 to 0.139, we found that when using band area at 2970 cm-1 as a probe integral, the MS values obtained via the 1H NMR method exhibited linear correlations (R2 > 0.98) with at least 16 integral ratios derived from their FTIR spectra. The optimal reference bands with high reliability are located at 3440 cm-1 and 1415 cm-1, with R2 exceeding 0.99 and a MS range of 0.17-1.92. The band at 2875 cm-1 is less affected by the trace moisture present in HPCS samples than the others. The results of the method validation demonstrated a mean recovery of 98.9 ± 2.8 % and an RSD below 10 %, suggesting a simple, robust, and highly accurate and precise method. This method could be extendable for the determination of the MS of insoluble HPCS derivatives and other hydroxypropylated polysaccharides.

Determination of dextranase activity using 3-methyl-2-benzothiazolinone hydrazone method: Substrate refinement and fast-dissolution, method development and validation.

A highly sensitive method has been developed for accurately measuring dextranase activity using 3-methyl-2-benzothiazolinone hydrazine. This method is based on the dextran refinement and fast-dissolving approach established in this study, as well as the assay method for enzymatic hydrolysates. The measurement parameters for the reducing sugar ends were optimized by examining the slope, intercept, R2, and time stability of the standard curve of glucose solutions containing dextran. Kinetic determination was utilized to optimize enzymatic parameters and validate the method, which was subsequently utilized for the analysis of toothpaste and mouthwash. The findings suggest that the enzymatic hydrolysis follows a zero-order reaction, laying a solid foundation for the end-point assay of dextranase activity. The results demonstrated a linear correlation within the measurement range (0.7-6.5 mU/mL), exhibiting good repeatability, high sensitivity and accuracy. This method outperformed the 3,5-dinitrosalicylic acid method and circumvented potential interference from other components in toothpaste and mouthwash.

A highly sensitive, accurate, and stable method for measuring pectin depolymerase activity.

Pectin depolymerase is widely utilized in various industrial sectors. However, the traditional methods for determining its enzymatic activity have limitations, such as cumbersome operations and a significant impact of enzyme solution dilution ratios on activity. The 3-methyl-2-benzothiazolinone hydrazone (MBTH) method can be employed to address these issues, but pectin precipitation and strong background commonly arise in this method. We have successfully overcome these challenges by employing a low-temperature and high-alkaline environment, and further optimized the reagent compositions and detection wavelength to improve the method. Consequently, enzyme hydrolysis follows a zero-order reaction within 60 min, which is helpful for the endpoint measurement of pectinase activity. The developed calibration curve for pectinase concentration and hydrolysis rate demonstrates linearity (R2 = 0.9945) within the range of 2.5-15.8 mU/mL of pectinase. This method exhibits high sensitivity, accuracy, and stability, making it suitable for routine determination of pectin depolymerase activity in research and applications.