Simultaneous Protonation and Metalation of a Porphyrin Covalent Organic Framework Enhance Photodynamic Therapy.

Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is limited by excited state quenching and low reactive oxygen species generation efficiency. Herein, we report a simultaneous protonation and metalation strategy to significantly enhance the PDT efficacy of a nanoscale two-dimensional imine-linked porphyrin-COF. The neutral and unmetalated porphyrin-COF (Ptp) and the protonated and metalated porphyrin-COF (Ptp-Fe) were synthesized via imine condensation between 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and terephthalaldehyde in the absence and presence of ferric chloride, respectively. The presence of ferric chloride generated both doubly protonated and Fe3+-coordinated porphyrin units, which red-shifted and increased the Q-band absorption and disrupted exciton migration to prevent excited state quenching, respectively. Under light irradiation, rapid energy transfer from protonated porphyrins to Fe3+-coordinated porphyrins in Ptp-Fe enabled 1O2 and hydroxyl radical generation via type II and type I PDT processes. Ptp-Fe also catalyzed the conversion of hydrogen peroxide to hydroxy radical through a photoenhanced Fenton-like reaction under slightly acidic conditions and light illumination. As a result, Ptp-Fe-mediated PDT exhibited much higher cytotoxicity than Ptp-mediated PDT on CT26 and 4T1 cancer cells. Ptp-Fe-mediated PDT afforded potent antitumor efficacy in subcutaneous CT26 murine colon cancer and orthotopic 4T1 murine triple-negative breast tumors and prevented metastasis of 4T1 breast cancer to the lungs. This work underscores the role of fine-tuning the molecular structures of COFs in significantly enhancing their PDT efficacy.

Phycobilisome's Exciton Transfer Efficiency Relies on an Energetic Funnel Driven by Chromophore-Linker Protein Interactions.

The phycobilisome is the primary light-harvesting antenna in cyanobacterial and red algal oxygenic photosynthesis. It maintains near-unity efficiency of energy transfer to reaction centers despite relying on slow exciton hopping along a relatively sparse network of highly fluorescent phycobilin chromophores. How the complex maintains this high efficiency remains unexplained. Using a two-dimensional electronic spectroscopy polarization scheme that enhances energy transfer features, we directly watch energy flow in the phycobilisome complex of Synechocystis sp. PCC 6803 from the outer phycocyanin rods to the allophycocyanin core. The observed downhill flow of energy, previously hidden within congested spectra, is faster than timescales predicted by Förster hopping along single rod chromophores. We attribute the fast, 8 ps energy transfer to interactions between rod-core linker proteins and terminal rod chromophores, which facilitate unidirectionally downhill energy flow to the core. This mechanism drives the high energy transfer efficiency in the phycobilisome and suggests that linker protein-chromophore interactions have likely evolved to shape its energetic landscape.

Horizontal Rafting Plate for Treatment of the Tibial Plateau Fracture.

OBJECTIVE: This study aimed to investigate the value of a horizontal rafting plate in treating tibial plateau fractures. METHODS: The data of 24 patients in whom a horizontal rafting plate was used to treat a tibial plateau fracture between October 2014 and January 2018 were retrospectively analyzed, including 16 males and 8 females, aged 21-63 years old, with an average of 40 ± 14.68 years. The fractures included 13 in the left knee and 11 in the right knee. The places where the horizontal rafting plate were used included the anterior margin of tibia, anterolateral tibia, and posterolateral tibia. All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the Rasmussen functional score. Computed tomography (CT) scanning and three-dimensional reconstruction were performed preoperatively and postoperatively, with the quality of reduction of the fractured articular surface clarified by the final follow-up. The flexion and extension abilities of the knee joint were also measured in the postoperative follow-up. RESULTS: Preoperative CT scanning showed that the gap of the tibial plateau was 8.00 ± 1.40 (5-24) mm. The heights of the fracture of the articular surface at all three sites during the final follow-ups were significantly different from the height before the surgery (P < 0.05). The vertical distance between the articular line and the highest point of the articular surface after reduction was 0.17 ± 0.05 mm. Anatomic reductions were obtained in 24 patients. The Rasmussen functional score after surgeries was 27.25 ± 0.94 points. Bony union was achieved in all the patients. According to the Rasmussen radiological criteria, the scores during the last follow-up were as follows: the total score was 13-18 points, with an average of 16.00 ± 1.72 points; the scores were excellent in 17 cases and good in seven cases. Therefore, 100% of results were excellent or good. No infection or fracture nonunion was found. CONCLUSION: Using a horizontal plate can be an effective method for treating special types of fractures of the tibial plateau, including the anterior margin and anterolateral and posterolateral tibial plateau, with satisfactory treatment efficacy.

Surgical Strategy for Anterior Tibial Plateau Fractures in Hyperextension Knee Injuries.

OBJECTIVE: The aim of the present study was to summarize the clinical characteristics, treatment strategies, and clinical results for anterior tibial plateau fractures caused by hyperextension injuries. METHODS: We performed a retrospective analysis of 26 cases of anterior tibial plateau fractures that were treated with open reduction and internal fixation from January 2016 to December 2019, including 16 men and 10 women, aged 26-68 years old, with an average age of 47 ± 12.5 years. According to the three-column theory classification, there were 16 cases of single-column fractures (9 cases of anteromedial fractures and 7 cases of anterolateral fractures), 3 cases of two-column fractures (anteromedial + anterolateral fractures), and 7 cases of three-column fractures. Options for the surgical approach included anteromedial, anterolateral, modified anterior median, and anterolateral + posteromedial incision. The implants included a T-shaped plate, an L-shaped plate, a horizontal plate, and a TomoFix plate. The surgical approach and fixation method were selected based on the characteristics of the anterior tibial fracture. The Rasmussen radiological criteria were used to evaluate the effects of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery. Medial and lateral stress tests, the Lachman test, and the pivot shift test were used to evaluate the stability of the knee joint. The range of knee motion was recorded. RESULTS: All cases were followed up for 12-24 months, with an average follow up of 15.7 months. The operation time was (148 ± 42) min; the intraoperative blood loss was (150 ± 50) mL. A total of 22 cases were anatomically reduced and 4 cases were well-reduced, and the compression reduction rate was 100%. According to the Rasmussen radiology scoring, 17 cases were excellent and 9 cases were good. The excellent and good rate was 100%. The fracture healing time was 3.3 months. There is no difference in fracture healing time for different fracture types. Both the Lachman and pivot shift test findings were normal in 24 patients and nearly normal in 2 patients. The posterior drawer test was normal in 25 patients and close to normal in 1 patient. The varus stress test was normal in 24 patients and nearly normal in 2 patients, while the valgus stress test was normal in 23 patients, nearly normal in 2 patients, and abnormal in 1 patient. The range of motion (ROM) was 100°-137°, with an average of 125° ± 11.7°. The Hospital for Special Surgery (HSS) knee score at the last follow up was 79-98 points, with an average of 87.54 ± 8.36 points; the results were excellent in 21 cases and good in 5 cases. Therefore, 100% of results were excellent or good. Two cases had superficial wound infections after the operation. The recovery of 2 patients with common peroneal nerve injury was poor. CONCLUSION: The appropriate surgical approach and fixation method were performed according to the different positions of the anterior tibial fracture and satisfactory results were obtained after surgery.

Surgical Treatment of Lateral Tibial Plateau Fractures Involving the Posterolateral Column.

OBJECTIVE: To summarize the indications and the clinical effects of a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach in the treatment of fractures of the lateral tibial plateau involving the posterolateral column. METHODS: Eleven patients with lateral tibial plateau fractures were included in the present study. The fractures were Schatzker type II or lateral platform fractures involving posterolateral column. The anterolateral combined posterolateral approach (lateral + posterolateral locking plate fixation) was applied in 7 patients and 4 patients underwent transfibular neck osteotomy (lateral + posterolateral locking plate fixation + 1/4 tubular plate edge fixation, fibular osteotomy with Kirschner wire tension band fixation, and hollow nail fixation for upper tibiofibular joint). All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last followup, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery (HSS). The Lachman test and the pivot-shift test were used to evaluate the anterior and posterior and rotational stability of the knee joint. The range of knee motion was recorded. RESULTS: Bone healing was achieved in all patients with fractures treated with a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach. At the last follow-up, both the Lachman test and the pivot-shift test results were negative. All patients had complete knee extension. For the combined anterolateral and posterolateral approach, the knee flexion angle was 110°-130°, with an average of 122.86° ± 7.56°. For the transfibular neck osteotomy approach, the knee flexion angle was 115°-130°, with an average of 120.00° ± 7.07°. For the patients in which the combined anterolateral and posterolateral approach was used, the Rasmussen score was 12-18 points, with an average of 16.00 ± 2.56 points. The results were excellent in 4 cases and good in 3 cases; therefore, 100% of results were excellent or good. For patients in which the transfibular neck osteotomy approach was used, the Rasmussen score was 10-18 points, with an average of 15.25 ± 3.77 points. The results were excellent in 2 cases, good in 1 case, and acceptable in 1 case; therefore, 75% of results were excellent or good. The HSS score for the combined anterolateral and posterolateral approach was 76-98 points, with an average of 88.43 ± 7.55 points. The results were excellent in 5 cases and good in 2 cases; therefore, 100% of results were excellent or good. The HSS score for the transfibular neck osteotomy approach was 74-96 points, with an average of 87.25 ± 9.43 points. The results were excellent in 3 cases and good in 1 case; therefore, 100% of results were excellent or good. There were no significant differences in operation time, surgical blood loss, fracture healing time, postoperative imaging score, and knee function evaluation between the two approaches. One patient who underwent transfibular neck osteotomy had a 3-mm step that gradually appeared, but no significant abnormalities were found in the width of the platform and the lower limb force line. One patient in whom the combined anterolateral and posterolateral approach was used showed numbness in the common peroneal nerve. No common peroneal nerve injury occurred through the transfibular neck osteotomy approach. CONCLUSIONS: The anterolateral combined posterolateral approach and the transfibular neck osteotomy approach are effective in the surgical treatment of lateral tibial plateau fractures involving the posterolateral column. However, the transfibular neck osteotomy approach is more suitable for the posterolateral plateau articular surface damaged with bone separation and displacement, deep collapse, cases involving a large range of the posterolateral column, especially fractures of the lateral tibial plateau in the upper tibiofibular syndesmosis area of the line connecting the anterior and posterior margin of the fibular head to the midpoint of the plateau.

JAB1 accelerates odontogenic differentiation of dental pulp stem cells.

Jun activation domain-binding protein 1 (JAB1) is a multifunctional protein that participates in the control of cell proliferation and the stability of multiple proteins. JAB1 regulates several key proteins, and thereby produces varied effects on cell cycle progression, genome stability and cell survival. Some studies have shown that the loss of JAB1 in osteochondral progenitor cells severely impairs embryonic limb development in mice. However, the biological significance of JAB1 activity in the odontogenic differentiation of dental pulp stem cells (DPSCs) remains unclear. This study aimed to determine the role of JAB1, a key player in tooth development, in reparative dentin formation, especially odontogenic differentiation. We found that increased expression of JAB1 promoted odontogenic differentiation of DPSCs via Wnt/ß-catenin signaling. The role of JAB1 in the odontogenic differentiation of DPSCs was further confirmed by knocking down JAB1. Our findings provide novel insights on odontogenic differentiation of DPSCs.

AGS3 is involved in TNF-α medicated osteogenic differentiation of human dental pulp stem cells.

Dental pulp stem cells (DPSCs) are multipotent adult stem cells capable of differentiating along the osteoblast, adipocyte, and chondrocyte lineages. Regulating differentiation of DPSCs may be a useful tool for regenerative medicine and cell-based therapy in oral diseases. Multisignaling pathways are involved in osteogenic differentiation of DPSCs. Recent studies show that cAMP/PKA/CREB signaling could stimulate the expression of genes such as bone morphogenic proteins 2 (BMP2), inhibitor of DNA binding 2 (ID2), bone sialoprotein, osteocalcin, and type XXIV collagen, which have been implicated in osteogenesis and bone formation. Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, plays an important role in regulating the phosphorylation of cyclic AMP response element-binding protein (p-CREB). However, the involvement of AGS3 in osteogenic differentiation of DPSCs has not been explored. Our data indicated that increased expression of AGS3 would inhibit osteogenic differentiation of DPSCs exposed to inflammatory cytokine tumor necrosis factor α (TNF-α) via cAMP/PKA/CREB signaling. The negative role of AGS3 in osteogenic differentiation was further confirmed by knocking down and over expression of AGS3. Our findings may provide clinical implications for osteoporosis.

RAC1 regulate tumor necrosis factor-α-mediated impaired osteogenic differentiation of dental pulp stem cells.

Human dental pulp contains a rapidly proliferative subpopulation of precursor cells termed dental pulp stem cells (DPSCs) that show self-renewal and multilineage differentiation, including neurogenic, chondrogenic, osteogenic and adipogenic. We previously reported that tomuor necrosis factor-α (TNF-α) (10 ng/mL) triggered osteogenic differentiation of human DPSCs via the nuclear factor-κB (NF-κB) signaling pathway. While previous studies showed that cells treated with TNF-α at higher concentrations showed decreased osteogenic differentiation capability. In this study we analyze the function of TNF-α (100 ng/mL) on osteogenic differentiation of human DPSCs for the first time and identify the underlying molecule mechanisms. Our data revealed that TNF-α with higher concentration significantly reduced mineralization and the expression of bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX2). Further, we revealed that TNF-α could suppress the osteogenic differentiation of DPSCs via increasing the expression of RAC1, which could activate the Wnt/ß-catenin signaling pathway and liberate ß-catenin to translocate into the nucleus. Genetic silencing of RAC1 expression using siRNA restored osteogenic differentiation of DPSCs. Our findings may provide a potential approach to bone regeneration in inflammatory microenvironments.

Expression of Peroxiredoxin 1 After Traumatic Spinal Cord Injury in Rats.

Reactive astrogliosis and microgliosis after spinal cord injury (SCI) contribute to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte and microglia proliferation upon injury remain partially understood. Peroxiredoxin 1 (PRDX1) is an antioxidant participating in cell proliferation, differentiation, and apoptosis. However, PRDX1 functions in SCI-induced astrocyte and microglia proliferation are unknown. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PRDX1 during the pathological process of SCI. We found the palpable expression increase of PRDX1 after SCI by western blot and immunohistochemistry staining. Double immunofluorescence staining showed that PRDX1 expression mainly increased in astrocytes and microglia. In addition, PRDX1/proliferating cell nuclear antigen (PCNA) colocalized in astrocytes and microglia. Furthermore, PCNA expression also elevated after SCI, as well as was positively correlated with PRDX1 expression. In vitro, PRDX1 expression in primary rat spinal cord astrocytes and microglia changed in a concentration- and time-dependent manner according to LPS treatment. In addition, PRDX1 knockdown in astrocytes and microglia resulted in the decrease of PCNA expression after LPS stimulation, showing that PRDX1 promoted astrocyte and microglia proliferation after inflammation. Our results suggested that PRDX1 might play a crucial role in astrocyte and microglia proliferation after SCI.

[Analyses of relevant influencing factors in the treatment of tibial pilon fractures].

OBJECTIVE: To explore the relevant influencing factors of surgical outcomes for closed tibial pilon fractures. METHODS: From April 2005 to May 2011, 52 consecutive closed tibial pilon fractures were treated by the same surgical team. There were 35 males and 17 females with a mean age of 40.0 years. According to the Ruedi-Allgower classification, the fracture types included type I (n = 13), type II (n = 22) and type III (n = 17). All patients were evaluated by the scores of American Orthopedic Foot and Ankle Society (AOFAS) and Burwell-Chamley. Postoperative complications were also recorded. The primary influencing factors of clinical outcomes were determined with regards to fracture types, reduction, complications and outcomes. RESULTS: The average follow-up period was 14.1 months (range: 6 - 28). The mean healing time was 5.5 months (range: 4.0 - 11). The reduction status: anatomical (n = 20), functional (n = 24) and poor (n = 8). Ankle function was excellent (n = 12), good (n = 26), fair (n = 9) and poor (n = 5). Incidence of complication was 30.8% (n = 16), including incision skin necrosis (n = 5), superficial soft tissue infection (n = 4), deep infection (n = 1) and posttraumatic arthrosis (n = 6). No significant differences (P > 0.05) existed in the occurrence of incision skin necrosis, superficial infection and deep infection between the outcomes of excellent/good and fair/poor groups while posttraumatic arthrosis rate had significant difference (P = 0.005) between two groups. The quality of reduction was an independent risk factor of final clinical outcomes. CONCLUSION: The quality of reduction, types of fracture and occurrence of posttraumatic arthrosis are risk factors of final outcomes for closed tibial pilon fractures.

Validity of the Chinese version Mood Disorder Questionnaire (MDQ) and the optimal cutoff screening bipolar disorders.

To investigate the validity of the Chinese version of Mood Disorder Questionnaire (C-MDQ) in China. Patients with bipolar disorders (BP, N=284) and patients with unipolar depressive disorder (UP, N=134) were assessed with the C-MDQ. The Eigenvalues of the first two factors were 3.15 and 2.09, respectively. The Cronbach's alpha of the C-MDQ was 0.79. The frequency of positive responses of UP patients was significantly lower than those of BP patients for 12 items except the seventh item. A C-MDQ screening score of seven or more was the best cutoff between BP and UP. The C-MDQ could distinguish between bipolar II disorder (BP-II) and UP, and the best cutoff was five. A cutoff of five had a sensitivity of 0.80 and a specificity of 0.54 between BP and UP. This study demonstrated the good validity of C-MDQ in China. The best cutoff between BP-II and UP can be regarded as the optimal cutoff between BP and UP to improve the sensitivity of screening for BP-II. Five should be the optimal cutoff between the BP and UP when only the 13 items of the questionnaire are used in China.

[Survey on mental disorders among registered residents and non-registered residents in Shenzhen].

OBJECTIVE: To study the prevalence and distribution of mental disorders among registered and non-registered residents in Shenzhen. METHODS: An epidemiological survey on mental disorders were carried out in Shenzhen by stratified multi-stage randomized sampling method; 7134 respondents were assessed through face-to-face interview, using the WHO standardized version on World Mental Health (WMH) Survey Initiative of the Composite International Diagnostic Interview (CIDI3.1). RESULTS: (1) The weighting prevalence of mental disorders was 21.87%. The prevalence of non-registered residents was significantly higher than that of the registered residents (22.34% vs. 19.99%; OR=1.15, 95%CI: 1.03-1.29; P<0.05) and the prevalence of females was significantly higher than that of males (22.68% vs. 19.67%; OR= 1.20, 95%CI: 1.07-1.34; P<0.05). The weighting prevalence of mood disorders, anxiety disorders and psychoses were 9.62%, 14.45% and 1.40%, respectively. (2) The weighting twelve-month incidence of mental disorders was 13.42%. The incidence of non-registered residents was significantly higher than that of the registered residents (13.80% vs. 11.90%; OR=1.19, 95%CI: 1.03-1.36; P<0.05). (3)The co-morbidity rate between mental disorders was 35.76%. (4)The prevalence and severity of mental disorders were associated with sex, household situation of registration, marital status, education, economic condition and occupation status. CONCLUSION: Mental disorders have become common diseases and serious public health problem in Shenzhen, with non-registered residents and females deserve more attention.

Assessing depressive symptoms in persons who die of suicide in mainland China.

BACKGROUND: The potential insensitivity to depression of translated diagnostic instruments makes it difficult to assess the relationship of depressive symptoms to suicide in non-Western cultures. METHODS: Addition of culturally sensitive probes and other modifications were made to the depression section of the Chinese version of the SCID; the standard SCID probes and the expanded-probes are separately used to assess each symptom of depression, the resultant diagnoses and the overall severity of depression. This modified SCID was included in the psychological autopsy interviews with family members and, separately, close associates of 887 suicides and 721 non-suicidal decedents from 23 regions of mainland China. RESULTS: Compared to the standard interview, the expanded-probe method increased reported prevalence of major depressive episode among suicide decedents from 26.4% (234/887) to 40.2% (357/887) and for other deaths from 1.0% (7/721) to 2.1% (15/701). The additional 131 cases identified using the expanded-probe method had substantial social impairment and a greatly elevated risk of suicide compared to those with no depressive symptoms (OR=37.0, 95% CI=17.6-77.6). Inter-observer reliability for major depressive episode between the two independent interviews was greater for the expanded probe method (ICC=0.77 vs. 0.67, P<0.001). For both interview methods there was a strong dose-response relationship between suicide risk and the number and severity of depressive symptoms. LIMITATIONS: This study uses proxy informants to obtain information about the psychological status of deceased subjects; the value of this expanded-probe method for the diagnosis of depression in non-Western cultures needs to be confirmed with living subjects. CONCLUSIONS: Adding culture-appropriate probes about depressive symptoms to standardized diagnostic instruments identifies many Chinese subjects with unrecognized depression. Dimensional measures of depressive symptoms are more powerful predictors of suicide risk than categorical diagnoses.

[Association study of five pedigree with high incidence of schizophrenia].

This study is to explore the relationship between polymorphism of Catechol O-methyltransferase gene and schizophrenia. Search for a gene predisposing to schizophrenia in the Han nationality in China. Five pedigrees with high incidence of schizophrenia were studied by polymerize chain reaction(PCR) and restriction fragment length polymorphism(RFLP) technique. Statistics analysis of the transmission/disequilibrium test (TDT) showed that the COMT gene is associated with schizophrenia in the five pedigree with high incidence schizophrenia(P=0.0455). The results suggest that there might have a schizophrenia liability gene on 22 chromosome (22q11.2) in our studied pedigrees.