Ultrabright Xanthene Fluorescence Probe for Mitochondrial Super-Resolution Imaging.

Mitochondria are important organelles that provide energy for cellular physiological activities. Changes in their structures may indicate the occurrence of diseases, and the super-resolution imaging of mitochondria is of great significance. However, developing fluorescent probes for mitochondrial super-resolution visualization still remains challenging due to insufficient fluorescence brightness and poor stability. Herein, we rationally synthesized an ultrabright xanthene fluorescence probe Me-hNR for mitochondria-specific super-resolution imaging using structured illumination microscopy (SIM). The rigid structure of Me-hNR provided its ultrahigh fluorescence quantum yield of up to 0.92 and ultrahigh brightness of up to 16,000. Occupying the para-position of the O atom in the xanthene skeleton by utilizing the smallest methyl group ensured its excellent stability. The study of the photophysical process indicated that Me-hNR mainly emitted fluorescence via radiative decay, and nonradiative decay and inter-system crossing were rare due to the slow nonradiative decay rate and large energy gap (ΔEst = 0.55 eV). Owing to these excellent merits, Me-hNR can specifically light up mitochondria at ultralow concentrations down to 5 nM. The unprecedented spatial resolution for mitochondria with an fwhm of 174 nm was also achieved. Therefore, this ultrabright xanthene fluorescence probe has great potential in visualizing the structural changes of mitochondria and revealing the pathogenesis of related diseases using SIM.

Polarity-Sensitive Probe for Two-Photon Fluorescence Lifetime Imaging of Lipid Droplets In Vitro and In Vivo.

Lipid droplets (LDs) are crucial organelles used to store lipids and participate in lipid metabolism in cells. The abnormal aggregation and polarity change of LDs are associated with the occurrence of diseases, such as steatosis. Herein, the polarity-sensitive probe TBPCPP with a donor-acceptor-π-acceptor (D-A-π-A) structure was designed and synthesized. The TBPCPP has a large Stokes shift (∼220 nm), excellent photostability, high LD targeting, and considerable two-photon absorption (TPA) cross-section (∼226 GM), enabling deep two-photon imaging (∼360 µm). In addition, the fluorescence lifetime of TBPCPP decreases linearly with increasing solvent polarity. Therefore, with the assistance of two-photon fluorescence lifetime imaging microscopy (TP-FLIM), TBPCPP has successfully achieved not only the visualization of polarity changes caused by LD accumulation in HepG-2 cells but also lipid-specific imaging and visualization of different polarities in lipid-rich regions in zebrafish for the first time. Furthermore, TP-FLIM revealed that the polarity gradually decreases during steatosis in HepG-2 cells, which provided new insights into the diagnosis of steatosis.

Vertebroplasty combined with facet joint block vs. vertebroplasty alone in relieving acute pain of osteoporotic vertebral compression fracture: a randomized controlled clinical trial.

OBJECTIVE: The study objective was to compare the efficacy and safety of percutaneous vertebroplasty (PVP) combined with facet joint block (FB) and vertebroplasty alone in relieving acute pain on osteoporotic vertebral compression fractures (OVCFs). METHODS: A prospective, randomized controlled study was conducted. One hundred ninety-eight patients of OVCFs undergoing surgery were randomly divided into two groups: Group P (PVP, n = 97), Group PF (PVP + FB, n = 101). The Visual analogue scale (VAS) and Oswestry disability index (ODI) were measured during pre-operation, 1 day, 1, 3, 6 and 12 months after the operation, respectively. The hospitalization time, operation time, complications, recurrence, the mean amount of cement injected and the number of patients who applied Cox-2 inhibitors within 3 days after operation were compared in the two groups. RESULTS: The VAS and ODI scores at each observation point of the post-operation were significantly decreased than that at the pre-operation in both groups (P < 0.05). The VAS and ODI scores in Group PF were significantly lower than that in Group P 1 day and 1 month after the operation (P < 0.05). The number of patients who applied Cox-2 inhibitors within 3 days after operation in group PF was significantly lower that in Group P (P < 0.001). There was no significant difference in hospitalization time, operation time, the mean amount of cement injected, complication rate, VAS and ODI scores at the pre-operation (P > 0.05). CONCLUSION: Both PVP combined with FB and PVP alone are effective treatment methods for OVCFs. But PVP combined with FB showed better back pain relief than PVP alone in the short term after the operation for OVCFs.

Comparison of clinical outcomes with proximal femoral nail anti-rotation versus bipolar hemiarthroplasty for the treatment of elderly unstable comminuted intertrochanteric fractures.

BACKGROUND: Although proximal femoral nail anti-rotation (PFNA) and bipolar hemiarthroplasty (BHA) are selected by most of the orthopaedic surgeons for elderly intertrochanteric fractures (ITFs) patients, there is still no consensus on the superiority of PFNA and BPH for the elderly with unstable comminuted ITFs. The study aims to compare the curative effects of PFNA and cementless BHA on unstable comminuted ITFs in the elderly. METHODS: From January 2012 to December 2016, we retrospectively reviewed 62 ITFs patients up to the inclusion and exclusion criteria in the study. Depending on the type of surgery, the patients were divided into two groups: Group BHA (n= 30) and Group PFNA (n = 32). The ITFs were classified according to Evans-Jensen. Hospitalization time, operation time, bleeding loss, weight bearing duration, Harris hip scores, 10-m walking speed, gait and postoperative complications were compared between the two groups. RESULTS: There was no significant difference between the groups in hospital stay (P > 0.05). The BHA group trended to have a shorter operation time and a larger volume of blood loss (P < 0.01).The weight bearing duration was shorter in the BHA group than the PFNA group (P < 0.05).The Harris hip score was higher, the 10-m walking speed was faster and the gait was better in group BHA than group PFNA at three months postoperatively (P < 0.05), but there was no significant difference between the two groups at 6 and 12 months postoperatively (P > 0.05). There was no significant difference in postoperative complications between the two groups (P > 0.05). CONCLUSION: The BHA allows an earlier return to weight-bearing activity, but ultimately has the same effective treatments as the PFNA for the elderly with unstable comminuted ITFs.

Transforaminal epidural steroid injection combined with radio frequency for the treatment of lumbar disc herniation: a 2-year follow-up.

BACKGROUND: To assess the therapeutic efficacy of transforaminal epidural steroid injection (TFESI) combined with radio frequency (RF) for the treatment of lumbar disc herniation (LDH). METHODS: A total of 230 patients participated in the study: TFESI (Group T, n = 110), TFESI combined with RF (Group TR, n = 120). Visual analogue scale (VAS), Oswestry disability index (ODI) and Global perceived effect (GPE) scale were measured pre-operation, 1, 3, 6, 12 and 24 months after the operation. Hospitalization time, treatment time, complications, and recurrence were compared between the two groups. RESULTS: The VAS and ODI at each observation point of the post-operation were significantly decreased compared with the pre-operation in both groups (P < 0.05). There was no statistically difference of VAS and ODI between the two groups at 1 and 3 months of the post-operation (P > 0.05). However, The VAS and ODI scores in Group TR were significantly lower than that in Group T at 6, 12 and 24 months of the post-operation (P < 0.05). The GPE in group TR was high in the early days, while that at 1 and 3 months after treatment was significantly higher than that in group T (P < 0.05). The recurrence rate in Group TR was lower than that in Group T (P = 0.002). There was no significant difference in hospitalization time, complications, VAS and ODI score at the pre-operation between the two groups (P > 0.05). CONCLUSION: These findings suggest that TFESI combined with RF could effectively improve the pain and function, and had a long-term satisfactory effect for the treatment of LDH.

All-Cellulose Nanofiber-Based Sustainable Triboelectric Nanogenerators for Enhanced Energy Harvesting.

Triboelectric nanogenerators (TENGs) show promising potential in energy harvesting and sensing for various electronic devices in multiple fields. However, the majority of materials currently utilized in TENGs are unrenewable, undegradable, and necessitate complex preparation processes, resulting in restricted performance and durability for practical applications. Here, we propose a strategy that combines straightforward chemical modification and electrospinning techniques to construct all-cellulose nanofiber-based TENGs with substantial power output. By using cellulose acetate (CA) as the raw material, the prepared cellulose membranes (CMs) and fluorinated cellulose membranes (FCMs) with different functional groups and hydrophobic properties are applied as the tribopositive and tribonegative friction layers of FCM/CM-based triboelectric nanogenerators (FC-TENGs), respectively. This approach modulates the microstructure and triboelectric polarity of the friction materials in FC-TENGs, thus enhancing their triboelectric charge densities and contact areas. As a result, the assembled FC-TENGs demonstrate enhanced output performance (94 V, 8.5 µA, and 0.15 W/m2) and exceptional durability in 15,000 cycles. The prepared FC-TENGs with efficient energy harvesting capabilities can be implemented in practical applications to power various electronic devices. Our work strengthens the viability of cellulose-based TENGs for sustainable development and provides novel perspectives on the cost-effective and valuable utilization of cellulose in the future.

A General Strategy for Enhanced Photodynamic Antimicrobial Therapy with Perylenequinonoid Photosensitizers Using a Macrocyclic Supramolecular Carrier.

Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram-negative bacteria and poor water solubility significantly restrict their potential in broad-spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water-soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host-guest complexes with high binding constants (≈107 m -1) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram-negative bacteria. As a result, the AnBox·4Cl-PQPS complexes can effectively anchor on the surfaces of gram-negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad-spectrum PDAT effect against both gram-negative and gram-positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs' water solubility and killing efficacy for gram-negative bacteria.

A glutathione responsive photosensitizer based on hypocrellin B for photodynamic therapy.

As a typical natural photosensitizer, hypocrellin B (HB) offers the advantages of high molar extinction coefficient, high phototoxicity, low dark toxicity, and fast metabolism in vivo. However, the lack of tumor specificity hinders its clinical applications. Herein, we designed and synthesized a glutathione (GSH) responsive photosensitizer based on HB. The 7 - nitro - 2,1,3 - benzoxadiazole (NBD) covalently connected to HB not only served as a fluorescence quenching group but also as a GSH activating group. The photosensitizer HB-NBD showed almost no fluorescence and singlet oxygen generation as a result of the photoinduced electron transfer between HB and NBD. The designed photosensitizer HB-NBD can be activated by GSH in solutions and cancer cells, and then obtain recuperative fluorescence and photosensitive activity.

Unilateral Biportal Endoscopic Discectomy versus Percutaneous Endoscopic Interlaminar Discectomy for Lumbar Disc Herniation.

Background: As the latest endoscopic spine surgery, percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) discectomy have distinct technical characteristics. This study aimed to evaluate the clinical outcomes of PEID and UBE discectomy in the treatment of single-level lumbar disc herniation (LDH). Methods: Between February 2019 and April 2022, 115 patients with single-level LDH at L4-5 or L5-S1 received PEID or UBE discectomy. The patients were separated into two groups based on the surgical method used: Group 1 (the PEID group) (n = 60) and Group 2 (the UBE group) (n = 55). Various parameters, including operative time, hospitalization time, fluoroscopy frequency, total costs, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI), were evaluated and compared between the two groups. Results: There were no significant differences in the VAS and ODI scores in 12 months after the operation between two groups (P > 0.05). However, the VAS of lower back pain on the first day after the operation in Group 2 (2.53±0.89) was higher than that in Group 1 (2.19±0.74) (P < 0.05). There were no significant differences in the operation time and incidence of complications between two groups (P > 0.05). But total costs in Group 2 (43,121±4280) were significantly higher than those in Group 1 (30,069±3551) (P < 0.05). Conclusion: Both UBE and PEID procedures have similar efficacy in alleviating pain and improving functional ability in patients with LDH. However, UBE surgery results in higher costs than PEID surgery.

Transcription factor B-MYB activates lncRNA CCAT1 and upregulates SOCS3 to promote chemoresistance in colorectal cancer.

Currently, resistance to oxaliplatin (OXA) has become an important obstacle to improving the clinical outcome of patients with colorectal cancer (CRC). Moreover, long non-coding RNAs (lncRNAs) have been documented in cancer chemoresistance, and our bioinformatic analysis suggested an involvement of lncRNA CCAT1 in CRC development. In this context, this study aimed to clarify the upstream and downstream mechanisms underpinning the effect of CCAT1 in the resistance of CRC to OXA. The expression of CCAT1 and the upstream B-MYB in the CRC samples was predicted by bioinformatics analysis and then verified using RT-qPCR in CRC cell lines. Accordingly, overexpression of B-MYB and CCAT1 was observed in CRC cells. SW480 cell line was used for the construction of OXA-resistant cell line (SW480R). Ectopic expression and knockdown experiments of B-MYB and CCAT1 were conducted in SW480R cells to delineate their roles in the malignant phenotypes and half-maximal (50%) inhibitory concentration (IC50) of OXA. It was found that CCAT1 promoted the resistance of CRC cells to OXA. Mechanistically, B-MYB transcriptionally activated CCAT1, which recruited DNMT1 to inhibit SOCS3 expression through elevating the SOCS3 promoter methylation. By this mechanism, the resistance of CRC cells to OXA was enhanced. Meanwhile, these in vitro findings were reproduced in vivo on xenografts of SW480R cells in nude mice. To sum up, B-MYB might promote the chemoresistance of CRC cells to OXA via regulating the CCAT1/DNMT1/SOCS3 axis.