Direct Population of Triplet States for Efficient Organic Afterglow through the Intra/Intermolecular Heavy-Atom Effect.

Organic afterglow is a fascinating phenomenon with exceptional applications. However, it encounters challenges such as low intensity and efficiency, and typically requires UV-light excitation and facile intersystem crossing (ISC) due to its spin-forbidden nature. Here, we develop a novel strategy that bypasses the conventional ISC pathway by promoting singlet-triplet transition through the synergistic effects of the intra/intermolecular heavy-atom effect in aromatic crystals, enabling the direct population of triplet excited states from the ground state. The resulting materials exhibit a bright organic afterglow with a remarkably enhanced quantum efficiency of up to 5.81%, and a significantly increased organic afterglow lifetime of up to 157 microseconds under visible light. Moreover, given the high-efficiency visible-light excitable organic afterglow emission, the potential application is demonstrated in lifetime-resolved, color-encoded, and excitation wavelength-dependent pattern encryption. This work demonstrates the importance of the direct population method in enhancing the organic afterglow performance and red-shifting the excitation wavelength, and provides crucial insights for advancing organic optoelectronic technologies that involve triplet states.

The learning-relative hemodynamic modulation of cortical plasticity induced by a force-control motor training.

Background: Novel motor skills are generally acquired through repetitive practices which are believed to be strongly related to neural plasticity mechanisms. This study aimed to investigate the learning-relative hemodynamic modulation of cortical plasticity induced by long-term motor training. Methods: An 8-day participation-control program was conducted. Eighteen right-handed healthy participants were recruited and randomly assigned into the training (12) and control groups (6). The training group were arranged to undergo the 8-day block-designed motor training which required to repeat a visuomotor force-control task. The functional near-infrared spectroscopy (fNIRS) was used to continuously monitor the cortical hemodynamic response during training. Two transcranial magnetic stimulation (TMS) measurements were performed before and after training to evaluate the cortical excitability changes. The transfer effects of learning were also investigated. Results: The behavior performance was quantified via score execution accuracy to illustrate the fast/slow learning stages as experience cumulated. The cortical hemodynamic activations mapped by fNIRS exhibited a temporal evolution trends that agreed the expansion-renormalization model, which assumed the brain modulation against skill acquisition includes complex mechanisms of neural expansion, selection, and renormalization. Functional connectivity (FC) analysis showed the FC strength was maintained, while the measured homodynamic activation returned to baseline after certain level of skill acquisition. Furthermore, the TMS results demonstrated a significant increase of motor evoked potential (MEP) on the targeted muscle for the trained participants, who significantly outperformed the untrained subjects in learning transfer investigation. Conclusion: The study illustrated the expansion-renormalization trends during continuous motor training, and relative analysis showed the functional connectivity enhancement may be maintained after amplitude renormalization of cortical hemodynamic activations. The TMS findings further gave an implication of neural facilitations on the descending motor pathway when brain activation returned to renormalization status after certain level of learning stages was achieved, and the learning can transfer to enhance the performance while encountering similar tasks.

The effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula.

BACKGROUND: To evaluate the effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula. METHODS: Fifty-nine healthy adult patients with a unilateral fracture of the tibia and fibula were randomly divided into an experimental group and a control group. The experimental group was given the self-made combined elastic compression device for the compression treatment of the affected limbs after the operation. The main endpoints included the convenience, safety, and effectiveness of the self-made modular elastic compression device for patients with a fracture of the tibia and fibula. RESULTS: There were 29 cases in the experimental group and 30 cases in the control group. There were no significant differences between the two groups in the general data: age, gender, fracture site, and cause of injury. The preoperative swelling elimination time was 3.3 ± 1.2 days, and the postoperative swelling elimination time was 3.1 ± 1.4 days in the experimental group; the preoperative swelling elimination time was 6.3 ± 1.2 days, and the postoperative swelling elimination time was 7.3 ± 1.2 days in the control group. The preoperative and postoperative swelling degree in the experimental group was shorter than those in the control group. The difference in the postoperative detumescence time between the experimental group (3.1 ± 1.4 days) and the control group (7.3 ± 1.2 days) was significant, and the total hospital stay was 8.1 ± 1.5 days in the experimental group and 13 ± 2.5 days in the control group with a statistical significance of P < 0.05. The change of discharge hemoglobin volume (11.2 ± 6.5 g/L) of the experimental group was lower than that of the control group (3.5 ± 1.2 days), the total drainage volume was 260 ± 50 ml, and the change of admission and discharge hemoglobin volume was 30.3 ± 10.4 g/L. Specifically, although the difference in the average hospital stay between the two groups was statistically significant, the difference was only 1 day, and the clinical difference was not significant. However, in the change of the cumulative drainage volume and hemoglobin volume, the experimental group that was given compression therapy was significantly lower than the control group with a statistical significance (P < 0.05). The pressure injury (4 cases) in the experimental group was significantly lower than that in the control group (8 cases) (P < 0.05). CONCLUSION: A modular combined elastic compression device in patients with a tibial and fibular fracture can significantly accelerate a patient's rehabilitation, shorten the hospital stay, reduce blood loss, relieve the patient's pain, and relieve the patient's social-economic burden during recovery.

The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing.

Objective: Epithelial cancers often originate from progenitor cells, while the origin of hepatocellular carcinoma (HCC) is still controversial. HCC, one of the deadliest cancers, is closely linked with liver injuries and chronic inflammation, which trigger massive infiltration of bone marrow-derived cells (BMDCs) during liver repair. Methods: To address the possible roles of BMDCs in HCC origination, we established a diethylnitrosamine (DEN)-induced HCC model in bone marrow transplanted mice. Immunohistochemistry and frozen tissue immunofluorescence were used to verify DEN-induced HCC in the pathology of the disease. The cellular origin of DEN-induced HCC was further studied by single cell sequencing, single-cell nested PCR, and immunofluorescence-fluorescence in situ hybridization. Results: Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs, and not from recipient mice. Furthermore, the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model. DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs. Conclusions: These results suggested that BMDCs are an important origin of HCC, which provide important clues to HCC prevention, detection, and treatments.

TNFα inhibitor C87 sensitizes EGFRvIII transfected glioblastoma cells to gefitinib by a concurrent blockade of TNFα signaling.

OBJECTIVE: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients. The mechanism behind this type of primary resistance is not well understood. The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem. METHODS: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs; real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines. ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib. Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells. Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors. RESULTS: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance. A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo. CONCLUSIONS: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.

Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque.

Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.

Immune mechanisms induced by an HSV-1 mutant strain: Discrepancy analysis of the immune system gene profile in comparison with a wild-type strain.

Herpes simplex virus is a prevalent pathogen of humans of various age groups. The fact that no prophylactic or therapeutic vaccine is currently available suggests a significant need to further investigate the immune mechanisms induced by the virus and various vaccine candidates. We previously generated an HSV-1 mutant strain, M3, with partial deletions in ul7, ul41 and LAT that produced an attenuated phenotype in mice. In the present study, we performed a comparative analysis to characterize the immune responses induced by M3 versus wild-type HSV-1 in a mouse model. Infection with wild-type HSV-1 triggered an inflammatory-dominated response and adaptive immunity suppression and was accompanied by severe pathological damage. In contrast, infection with M3 induced a systematic immune response involving full activation of both innate and adaptive immunity and was accompanied by no obvious pathological changes. Furthermore, the immune response induced by M3 protected mice from lethal challenge with wild-type strains of HSV-1 and restrained virus proliferation and impaired latency. These data are useful for further HSV-1 vaccine development using a mutant strain construction strategy.

RNA gene profile variation in peripheral blood mononuclear cells from rhesus macaques immunized with Hib conjugate vaccine, Hib capsular polysaccharide and TT carrier protein.

BACKGROUND: The Haemophilus influenzae type b (Hib) conjugate vaccine has been widely used in children to prevent invasive Hib disease because of its strong immunogenicity and antibody response induction relative to the capsular polysaccharide (CPS) antigen. The data from vaccine studies suggest that the conjugate vaccine contains carrier proteins that enhance and/or regulate the antigen's immunogenicity, but the mechanism of this enhancement remains unclear. METHODS: To explore the immunological role of the conjugate vaccine, we compared the immune responses and gene profiles of rhesus macaques after immunization with CPS, carrier protein tetanus toxoid (TT) or conjugate vaccine. RESULTS: A distinct immune response was induced by the Hib conjugate vaccine but not by CPS or carrier protein TT. The genes that were dynamically regulated in conjunction with the macaque immune responses to the conjugate vaccine were investigated. CONCLUSIONS: We propose that these genes are involved in the induction of specific immunity that is characterized by the appearance and maintenance of antibodies against Hib.