Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

ABSTRACT: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

Incorporation of cross-linked/acetylated tapioca starches on the gelling properties, rheological behaviour, and microstructure of low-salt myofibrillar protein gels: Perspective on phase transition.

This study investigated the gelling properties, rheological behaviour, and microstructure of heat-induced, low-salt myofibrillar protein (MP) gels containing different levels (2%, 4%, 6%, and 8%, w/w) of cross-linked (CTS) or acetylated (ATS) tapioca starch. The results indicated that either CTS or ATS significantly enhanced the gel strength and water-holding capacity of low-salt MP gels (P < 0.05), an outcome verified by the rheological behaviour test results under different modes. Furthermore, iodine-staining images indicated that the MP-dominated continuous phase gradually transited to a starch-dominated phase with increasing CTS or ATS levels, and 4% was the critical point for this phase transition. In addition, hydrophobic interactions and disulphide bonds constituted the major intermolecular forces of low-salt MP gels, effectively promoting phase transition. In brief, modified tapioca starches possess considerable potential application value in low-salt meat products.

Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery.

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.

Influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions on the rheological and physicochemical properties of myofibrillar protein gels.

The study aimed to investigate the influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions (HIPPE) at different levels (0%, 10%, 20%, 30%, 40%, and 50%) on the rheological and physicochemical properties of myofibrillar protein (MPs) gels. The study indicated that with increasing HIPPE levels, there was a significant increase in whiteness while a decrease in water-holding capacity. The gels with 10% HIPPE levels had higher ionic bonds, while those with 40% and 50% HIPPE levels showed higher hydrogen bonds. By increasing HIPPE levels in the formation of MP gels, the T2 relaxation time was found to decrease. Additionally, in all MP gels, G' values were significantly higher than G" values over time. Adding lower contents of HIPPE levels resulted in a more compact microstructure. These findings indicate that flaxseed-derived diglyceride-based HIPPEs could be utilized as fat substitutes in meat products to enhance their nutritional quality.

Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

Myofibrillar protein hydrolysis under hydroxyl radical oxidative stress: Structural changes and their impacts on binding to selected aldehydes.

In this study, a hydroxyl radical oxidation system was established to simulate the oxidation process in fermented meat products. This system was employed to examine the structural changes in myofibrillar proteins (MPs) resulting from tryptic hydrolysis after a hydroxyl radical oxidative regime. The effect of these changes on the ability of MPs to bind selected aldehydes (3-methyl butanal, pentanal, hexanal, and heptanal) was also investigated. Moderate oxidation (H2O2 ≤ 1.0 mM) unfolded the structure of MPs, facilitating trypsin-mediated hydrolysis and increasing their binding capacity for the four selected aldehydes. However, excessive oxidation (H2O2 ≥ 2.5 mM) led to cross-linking and aggregation of MPs, inhibiting trypsin-mediated hydrolysis. The oxidised MPs had the best binding capacity for heptanal. The interaction of the oxidised trypsin-hydrolysed MPs with heptanal was driven by hydrophobic interactions. The binding of heptanal affected the structure of the oxidised trypsin-hydrolysed MPs and reduced their α-helix content.

The fusion gene LRP1-SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma.

Through transcriptome sequencing, we previously identified a new osteosarcoma-specific, frequent fusion gene, LRP1-SNRNP25, and found that it played an important role in tumor cell invasion and migration. However, the specific mechanism remains unclear. In this article, whole-genome sequencing further confirmed that the LRP1-SNRNP25 fusion gene is formed by fusion of LRP1 exon 8 and SNRNP25 exon 2. In vitro, scratch and Transwell assays demonstrated that the migration and invasion abilities of LRP1-SNRNP25-overexpressing osteosarcoma cells were significantly increased. To explore the molecular mechanism of the LRP1-SNRNP25 fusion in affecting osteosarcoma cell migration and invasion, we evaluated the migration and invasion-related molecular signaling pathways by western blotting. Some migration- and invasion-related genes, including pJNK and MMP2, were upregulated. Coimmunoprecipitation-mass spectrometry showed that 37LRP can interact with pJNK. Western blotting confirmed that LRP1-SNRNP25 overexpression upregulates 37LRP protein expression. Immunofluorescence staining showed the intracellular colocalization of LRP1-SNRNP25 with pJNK and 37LRP proteins and that LRP1-SNRNP25 expression increased the pJNK and 37LRP levels. Coimmunoprecipitation (co-IP) confirmed that LRP1-SNRNP25 interacted with pJNK and 37LRP proteins. The pJNK inhibitor SP600125 dose-dependently decreased the pJNK/37LRP/MMP2 levels. After siRNA-mediated 37LRP knockdown, the MMP2 protein level decreased. These two experiments proved the upstream/downstream relationship among pJNK, 37LRP, and MMP2, with pJNK the farthest upstream and MMP2 the farthest downstream. These results proved that the LRP1-SNRNP25 fusion gene exerts biological effects through the pJNK/37LRP/MMP2 signaling pathway. In vivo, LRP1-SNRNP25 promoted osteosarcoma cell growth. Tumor growth was significantly inhibited after SP600125 treatment. Immunohistochemical analysis showed that the pJNK, MMP2, and Ki-67 protein levels were significantly increased in tumor tissues of LRP1-SNRNP25-overexpressing cell-injected nude mice. Furthermore, lung and liver metastasis were more prevalent in these mice. In a word, LRP1-SNRNP25 promotes invasion, migration, and metastasis via pJNK/37LRP/MMP2 pathway. LRP1-SNRNP25 is a potential therapeutic target for LRP1-SNRNP25-positive osteosarcoma.

Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

Inhibition Effect of Non-Host Plant Volatile Extracts on Reproductive Behaviors in the Diamondback Moth Plutella xylostella (Linnaeus).

The pest management of Plutella xylostella, the global pest of cruciferous plants, is primarily dependent upon continued applications of insecticides, which has led to severe insecticide resistance and a series of ecological concerns. The essential oils (EOs) of non-host plants are considered to have a high application potential in pest behavioral control. In P. xylostella, the insecticidal properties, antifeeding activities, and oviposition inhibition effects of many EOs have been studied in larvae and female moths. However, less focus has been placed on the inhibitory effect on sex pheromone communication during courtship, which is vital for the reproduction of the offspring. In this study, by combining electrophysiological studies, laboratory behavioral assays, and field traps, we demonstrated that non-host plant EOs significantly inhibited the reproductive behaviors of both sexes. Notably, the calamus (Acorus gramineus) EO inhibited the preference of male moths for synthetic sex pheromone blends and reduced the egg-laying number of female moths on host plants, with the highest inhibition rates of 72% and 100%, respectively, suggesting a great application prospect of calamus and its EO on the behavioral control strategies of P. xylostella.

The roles of 5-HT in orofacial pain.

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

Vectorial holography over a multimode fiber.

Vectorial holography through a strongly scattering medium can facilitate various applications in optics and photonics. However, the realization of vectorial holography with arbitrary distribution of optical intensity is still limited because of experimental noise during the calibration of vectorial transmission matrix (TM) and reconstruction noise during the retrieval of input wavefront for a given holographic target. Herein, we propose and experimentally demonstrate the vectorial holography with arbitrary distribution of optical intensity over a multimode fiber (MMF) using the Tikhonov regularization. By optimizing the noise factor, the performance of vectorial holography over an MMF is improved compared with the conjugate transpose and inverse TM methods. Our results might shed new light on the optical communication and detection mediated by MMFs.

Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study.

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma.

Immunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that effective nivolumab treatment led to an upregulation of C2 levels, and higher levels following treatment are indicative of a good outcome. Through bioinformatics analyses and immunofluorescence, we identified a correlation between C2 and M1 macrophages. To further investigate the role of C2 in melanoma, we constructed subcutaneous tumorigenic models in C57BL/6 mice. The tumors in the C2 overexpression group exhibited significantly smaller sizes. Flow cytometric analysis of the mouse tumors demonstrated enhanced recruitment of macrophages, particularly of the M1 subtype, in the overexpression group. Moreover, single-cell RNA sequencing analysis revealed that C2-positive tumor cells exhibited enhanced communication with immune cells. We co-cultured tumor cell supernatants with macrophages in vitro and observed the induction of M1 subtype polarization. In addition, we discovered a close correlation between C2 and tertiary lymphoid structures. C2 has been demonstrated to exert a protective effect, mediated by its ability to modulate the tumor microenvironment. C2 serves as a prognostic marker for melanoma and can be employed to monitor the efficacy of immunotherapy.

Combined effects of high-intensity ultrasound treatment and hydrogen peroxide addition on the thermal stabilities of myofibrillar protein emulsions at low ionic strengths.

In this study, the effects of high-intensity ultrasound (HIU) treatment combined with hydrogen peroxide (H2O2) addition on the thermal stability of myofibrillar protein (MP)-stabilized emulsions in low-salt conditions were investigated. Results showed that compared to using either HIU or H2O2 treatment alone, HIU treatment combined with H2O2 was most effective in enhancing the physical stability of emulsions. Moreover, the emulsion stabilized by MPs co-treated with HIU and H2O2 exhibited the most uniform distribution, highest absolute zeta potential, and optimal rheological properties upon heating. This combination effect during heating was caused by the inhibition of disulfide bond cross-linking of myosin heads by H2O2 and the dissociation of filamentous myosin structures using the HIU treatment. In addition, the results of oxidative stability analysis indicated that the addition of H2O2 increased the content of oxidation products; however, the overall influence on the oxidative stability of emulsions was not significant. In conclusion, the combination of HIU and H2O2 treatment is a promising approach to suppress heat-induced MP aggregation and improve the thermal stability of corresponding emulsions.

Effect of flaxseed-derived diglyceride-based high internal phase Pickering emulsion on the quality characteristics of reformulated beef burgers.

The study aimed to fabricate healthier beef burgers using high internal phase Pickering emulsion (HIPPE) as animal fat substitute. In this context, HIPPE stabilized by modified soy protein isolates was produced with flaxseed-derived diglycerides (DAGs). Beef burgers were prepared by substituting beef backfat with HIPPE at varying levels (0%, 25%, 50%, 75%, and 100%). Reformulated burgers showed a significant decrease in WHC (from 89.75 to 77.38%), pH (from 5.73 to 5.58), L* values (from 53.5 to 44.5), and b* values (22.9 to 21.8), while a significant increase in a* values (from 24.4 to 6.7), cooking loss (from 20.25 to 30.62), and cooking shrinkage (from 11.27 to 13.05). Texture attributes, including hardness, chewiness, and gumminess, decreased up to 50% fat substitution and increased with increasing levels of fat substitution. Moreover, the rheological properties (G' and G'') and T2 relaxation time were increased with increasing fat replacement. The reformulation with HIPPE resulted in a decrease in SFA (from 3896 to 1712 mg/100 g), ω-6/ω-3 ratio (from 5.29 to 0.47), atherogenic index (from 0.57 to 0.13), and thrombogenic index (from 1.46 to 0.15) and increase in PUFA/SFA ratio (from 0.20 to 2.79). Notably, burgers with 50% fat substitution were more preferred regarding tenderness, while those with 100% fat substitution obtained higher scores for color and flavor than all other treatments. In conclusion, 50% fat replacement using flaxseed-derived diglyceride-based HIPPE improved beef burgers' textural profile and fatty acid composition without compromising the sensory characteristics.

Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

Electrochemical Visualization of Single-Molecule Thiol Substitution with Nanopore Measurement.

Reactions involving sulfhydryl groups play a critical role in maintaining the structure and function of proteins. However, traditional mechanistic studies have mainly focused on reaction rates and the efficiency in bulk solutions. Herein, we have designed a cysteine-mutated nanopore as a biological protein nanoreactor for electrochemical visualization of the thiol substitute reaction. Statistical analysis of characteristic current signals shows that the apparent reaction rate at the single-molecule level in this confined nanoreactor reached 1400 times higher than that observed in bulk solution. This substantial acceleration of thiol substitution reactions within the nanopore offers promising opportunities for advancing the design and optimization of micro/nanoreactors. Moreover, our results could shed light on the understanding of sulfhydryl reactions and the thiol-involved signal transduction mechanisms in biological systems.

Non-orthogonal optical multiplexing empowered by deep learning.

Orthogonality among channels is a canonical basis for optical multiplexing featured with division multiplexing, which substantially reduce the complexity of signal post-processing in demultiplexing. However, it inevitably imposes an upper limit of capacity for multiplexing. Herein, we report on non-orthogonal optical multiplexing over a multimode fiber (MMF) leveraged by a deep neural network, termed speckle light field retrieval network (SLRnet), where it can learn the complicated mapping relation between multiple non-orthogonal input light field encoded with information and their corresponding single intensity output. As a proof-of-principle experimental demonstration, it is shown that the SLRnet can effectively solve the ill-posed problem of non-orthogonal optical multiplexing over an MMF, where multiple non-orthogonal input signals mediated by the same polarization, wavelength and spatial position can be explicitly retrieved utilizing a single-shot speckle output with fidelity as high as ~ 98%. Our results resemble an important step for harnessing non-orthogonal channels for high capacity optical multiplexing.