A molecular container providing supramolecular protection against acetylcholine hydrolysis.

Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene.

We synthesized a new tetraphenylethylene-modified chitosan bioconjugate, CS-TPE, that shows the aggregation-induced emission effect. It can self-assemble into fluorescent polymeric nanoparticles in an aqueous solution at pH 5.3 either alone or with the water-soluble bowl-shaped six-fold carboxylated tribenzotriquinacene derivative TBTQ-C6 via host-guest binding. The spherical nanoparticles formed by CS-TPE amphiphiles or TBTQ-C6/CS-TPE supra-amphiphiles disintegrated under alkaline stimulation at pH 10.4 and the dispersion of the aggregates after the collapse in the presence of TBTQ-C6 was greatly improved. In addition, the fluorescence of CS-TPE was significantly enhanced by introducing TBTQ-C6, and remained relatively stable with variations in pH for both CS-TPE and TBTQ-C6/CS-TPE. Such pH-responsive supramolecular spherical nanoparticles with stable fluorescence emission based on CS-TPE or TBTQ-C6/CS-TPE may find applications in various fields, including the development of visual oral drug delivery systems.

pH-Responsive supramolecular vesicles for imaging-guided drug delivery: Harnessing aggregation-induced emission.

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt, TBTQ-C 6 , acts as the host component (H) forming host-guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives, G1 and G2, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells in vitro. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.

Cognitive Phenotype Shifts in Risk Taking: Interplay of Nonsuicidal Self-Injury Behaviors and Intensified Depression.

BACKGROUND: Nonsuicidal self-injury (NSSI) behavior is significantly prevalent in both adolescents and psychiatric populations, particularly in individuals with major depressive disorder. NSSI can be considered a result of risky decision making in response to negative emotions, where individuals choose self-harm over other less harmful alternatives, suggesting a potential decision-making deficit in those engaging in NSSI. This study delves into the complex relationship between NSSI and depression severity in decision making and its cognitive underpinnings. METHODS: We assessed decision behaviors in 57 patients with major depressive disorder and NSSI, 42 patients with major depressive disorder without NSSI, and 142 healthy control participants using the Balloon Analog Risk Task, which involves risk taking, learning, and exploration in uncertain scenarios. Using computational modeling, we dissected the nuanced cognitive dimensions influencing decision behaviors. A novel statistical method was developed to elucidate interaction effects between NSSI and depression severity. RESULTS: Contrary to common perceptions, we found that individuals with NSSI behaviors were typically more risk averse. There was also a complex interaction between NSSI and depression severity in shaping risk-taking behaviors. As depressive symptoms intensified, the individuals with NSSI began to perceive less risk and behave more randomly. CONCLUSIONS: This research provides new insights into the cognitive aspects of NSSI and depression, highlighting the importance of considering the influence of comorbid mental disorders when investigating the cognitive underpinnings of such behaviors, especially in the context of prevalent cross-diagnostic phenomena such as NSSI behaviors.

Prediction From Minimal Experience: How People Predict the Duration of an Ongoing Epidemic.

People are known for good predictions in domains they have rich experience with, such as everyday statistics and intuitive physics. But how well can they predict for problems they lack experience with, such as the duration of an ongoing epidemic caused by a new virus? Amid the first wave of COVID-19 in China, we conducted an online diary study, asking each of over 400 participants to predict the remaining duration of the epidemic, once per day for 14 days. Participants' predictions reflected a reasonable use of publicly available information but were meanwhile biased, subject to the influence of negative affect and future time perspectives. Computational modeling revealed that participants neither relied on prior distributions of epidemic durations as in inferring everyday statistics, nor on mechanistic simulations of epidemic dynamics as in computing intuitive physics. Instead, with minimal experience, participants' predictions were best explained by similarity-based generalization of the temporal pattern of epidemic statistics. In two control experiments, we further confirmed that such cognitive algorithm is not specific to the epidemic scenario and that minimal and rich experience do lead to different prediction behaviors for the same observations. We conclude that people generalize patterns in recent history to predict the future under minimal experience.

[The Prognosis and Predictive Value of Complement C3 in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effect of complement C3 on the prognosis of patients with multiple myeloma (MM), and to establish a predictive model to evaluate the overall survival. METHODS: Eighty newly diagnosed MM patients were enrolled, and clinical characteristics, such as sex, age, platelet count, white blood cell count, ISS stage, FISH, levels of kappa and lammda chain, complement C3 and C4 were retrospectively analyzed. Cox regression model was used for univariate and multivariate analysis about risk factors that affecting the prognosis of the MM patients. A nomogram based on C3 level was established for predicting the prognosis of MM patients. RESULTS: The average age of the MM patients was 63.15±10.41, including 36 males and 44 females. The median overall survival (OS) was 36.3 months, and the median progression-free survival (PFS) was 35.2 months, the 3-year OS rate and PFS rate of the MM patients were 67.5% and 52.5%, respectively. The variants selected by univariate analysis were put into multivariate regression model, the result showed that C3 level ≥0.7 U/L and PLT count <100×109/L were the independent risk factors for OS. Nomogram based on C3 level, PLT count as well as ß2-protein level showed an excellent accuracy in estimating prognosis of MM (C-index: 0.775). CONCLUSION: Patients with C3 level≥0.7 U/L or PLT count <100×109/L show poor prognosis. Nomogram based on the two variants can estimate overall survival of MM patients and provide suggestions to clinical decision.

Bilateral anterior cerebral artery occlusion following CD19- and BCMA-targeted chimeric antigen receptor T-cell therapy for a myeloma patient.

Chimeric antigen receptor T (CAR-T)-cell therapy is a promising treatment for relapsed/refractory multiple myeloma (RRMM). In our previous report, CD19- and BCMA-targeted CAR-T co-administration was associated with a high response rate. Although cytokine release syndrome (CRS) and neurotoxicity are frequent complications following CAR-T treatment, cerebral infarction is rarely reported as a CAR-T-related complication. We reported a 73-year-old female MM patient who received CD19- and BCMA-targeted CAR-T for refractory disease. Her disease responded to CAR-T therapy, but she developed neurological symptoms following CRS. Cranial CT and MRI demonstrated multiple cerebral infarctions and bilateral anterior cerebral artery (ACA) occlusion. We suggest that cerebral infarction other than CAR-T-related neurotoxicity is the underlying cause of abnormal neuropsychological symptoms, and diagnostic imaging tests should be actively performed to exclude ischemic cerebrovascular events.

[Survival and Prognosis Analysis of 57 Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship of clinical related indicator levels and clinical staging with the prognosis of MM patients so as to more accurately evaluate the disease status and guide the clinical treatment. METHOD: The clinical indicators including age, WBC and Plt counts, FISH result, ISS staging, Kappa and Lammada light chain levels and so on in 57 cases of MM were analyzed retrospectively; the unvariate and multivatiate analyses of factors influencing the prognosis of MM patients were performed by Kaplan-Meier and Cox regression model; the factors influencing the prognosis of patients were evaluated. RESULTS: Median age of 57 patients including 25 male and 32 female, was 63(29-81) years old, mean OS time was 37.3 months, mean PFS time was 36.3 months, 3-year OS and PFS were 73.6% and 56.1% respectively. The unvaviate analysis showed that age, WBC count, Plt count, FISH result, ISS staging, Kappa and lammda light chain levels, and remission were factors influencing the prognosis; the multivatiate analysis showed that the Kappa light chain level ≥19.4 mg/L and Plt count <100×109/L were independant risk factors influencing the prognosis of MM patients. CONCLUSION: The prognosis of MM patients with high Kappa light chian level and low Plt count is very poor, therefore the therapeutic regimens should be selected differentially for this kind of newly diagnosed MM patients so as to enhance the survival time of patients.

[Therapeutic Efficacy of Multigly-Cosidorum Tripterygium Combined with rhIL-11 for Immune Thrombocytopenia].

OBJECTIVE: To study the therapeutic efficacy of multigly-cosidorum Tripterygium combined with rhIL-11 for treating patients with immune thrombocytopenia (ITP). METHODS: A total of 75 patients with ITP were divided into 2 group: experimental group and control group. The experimental group included 40 patients who had been treated with multigly-cosidorum Tripterygium combined with rhIL-11. Multigly-cosidorum Tripterygium was given at a dose of 1mg/kg·d for 2 months and rhIL-11 was injected at a dose of 16,000,000 units per day. Control group included 35 patients who had been treated with prednisone at a dose of 1 mg/kg·d. Platelet counts were performed every day before platelet counts >30 × 109/L. Peripheral blood T cells were collected before and after treated for 2 months. The ratios of CD4⁺, CD8⁺ T cells in peripheral blood T cells were analyzed by flow cytometry. RESULTS: Totally effective rate in experimental group was 77.5%. Totally effective rate in control group was 82.9%. Totally effective rate showed no statistical difference between these two groups (P > 0.05). The average time of platelet count 30 × 109/L in experimental and control groups were 13.06 ± 6.10 days and 9.76 ± 5.71 days respectively; in experimental group, the ratio of CD4⁺ T cells in peripheral blood was 21.03% before treatment, then rised to 34.49% after treatment for 2 months (P < 0.01); The ratio of CD8⁺ T cells in peripheral blood was 26.35% before treatment, then decreased to 20.18% (P < 0.01). In control group, the ratio of CD4⁺ T cells was 22.30% before treatment, then rised to 25.11% after treatment for 2 months (P < 0.05); The ratio of CD8⁺ T cells in peripheral blood was 27.24% before treatment, then decreased to 21.35% (P < 0.01). CONCLUSION: Multigly-cosidorum tripterygium can correct disorder of T lymphocytes, the combination of multigly-cosidorum triptergium and rhIL-11 can accelerate therapeutic efficacy for treating ITP and with less adverse reaction, so this combination may be effective and safe for treating patients with ITP.

[Expression of integrins in bone marrow mesenchymal stem cells derived from patients with chronic myeloid leukemia].

The purpose of this study was to investigate the growth characteristics and the expression level of integrin mRNA of the cultured bone marrow mesenchymal stem cells (BMMSCs) from patients with chronic myeloid leukemia (CML) in myeloid crisis (MC), and explore the role of BMMSCs in pathogenesis of CML. Five CML patients were enrolled in experimental group, five healthy persons were used as control. BMMSCs were cultured in vitro. The morphology of BMMSCs was observed every day and the growth curve were portrayed, and the ability of cell proliferation were detected according to the daily results of cell counting. Total RNA was extracted from third and fourth passages of BMMSCs, The expression of integrins mRNA of BMMSCs were measured by real-time PCR. The results showed that the BMMSCs of experimental and control groups had no difference in growth characterisctics, but the expression of integrins mRNA of the BMMSCs was higher in CML patients than in normal control group (p < 0.05). It is concluded that the abnormally high expression of integrins of BMMSC from the CML patients take part in pathogenesis of CML.

Toward quartz and cristobalite: spontaneous resolution, structures, and characterization of chiral silica-mimetic silver(I)-organic materials.

An alpha-quartz-mimetic chiral coordination network of [Ag(L1)(CF3SO3)]n (L1=5,5'-bipyrimidine), after treatment with PF6- anions, undergoes a solution-state structural transformation toward [Ag(L1)(PF6)]n with a cristobalite-mimetic chiral structures. This structural transformation is accompanied by substantial enhancement in the fluorescent intensity and in the second-harmonic-generation response. The results also demonstrate an effective design strategy based on the spontaneous resolution route for the preparation of chiral architectures.

Influence of water content on the self-assembly of metal-organic frameworks based on pyridine-3,5-dicarboxylate.

A 0D discrete molecule [Co(3,5-pdc)(H2O)5].2H2O (1) was obtained in quantitative yield from the reaction of CoCl2.6H2O and pyridine-3,5-dicarboxylate (3,5-pdc) in pure water solvent at ambient temperature. While a 1D zigzag chain species, [{Co(3,5-pdc)(H2O)4}.H2O]n (2), was produced in a water-rich environment, a 2D layer compound, [Co(3,5-pdc)(H2O)2]n (3), with a 6(3) topology was generated under a water-reduced condition and a 2D sheet structure, [{Cu(3,5-pdc)(py)2}.H2O.EtOH]n (4), was formed under a water-poor condition. Compounds 1, 2, and 4 were characterized by single-crystal X-ray diffraction analysis. The 1D zigzag chain 2 shows a recoverable collapsing property. Compound 4 adopts a 2D sheet structure with a 4.8(2) topology, observed for the first time for the 3,5-pdc-related metal-organic frameworks. Water content was found to be an important factor in determining the topologies of the products in the self-assembly of divalent metal ions (Co2+, Cu2+) and pyridine-3,5-dicarboxylate under mild conditions.

[Cd(II)(bpdc).H(2)O](n): a robust, thermally stable porous framework through a combination of a 2-D grid and a cadmium dicarboxylate cluster chain (H(2)bpdc = 2,2'-Bipyridyl-4,4'-dicarboxylic acid).

The synthesis and characterization of a cadmium(II) coordination polymer, [Cd(C(12)H(6)N(2)O(4)) x H(2)O](n)() (1), is reported. A single-crystal X-ray analysis shows that compound 1 presents a non-interpenetrating three-dimensional porous host containing one-dimensional hydrophilic channels, where guest water molecules reside. The strategy in designing the 3-D framework architecture is based on a combination of two building subunits: a porous two-dimensional grid of (4,4) topology and a metal dicarboxylate cluster chain. Both subunits are assembled from the coordination of a cadmium ion with a three-connecting organic modular ligand, 2,2'-bipyridyl-4,4'-dicarboxylic acid (H(2)bpdc). The results of thermogravimetric analysis and powder X-ray diffraction study show that the framework rigidity of compound 1 remains intact upon the removal of guest molecules, and maintains the thermal stability up to 440 degrees C. The second-row transition-metal ions are capable of engaging higher coordination modes (e.g., hepta- and octacoordination) because of their atomic sizes and intrinsic electron configurations. Our results show that the heptacoordinated cadmium center plays an important role in the overall framework rigidity and high thermal stability of compound 1. Crystal data for 1: Cd(C(12)H(6)N(2)O(4)) x H(2)O, triclinic, space group P1 macro, a = 6.7843(5) A, b = 9.3299(7) A, c = 9.4439(7) A, alpha = 104.629(1) degrees, beta = 92.324(1) degrees, gamma = 100.416(1) degrees, Z = 2.