High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Objective To explore the difference in left ventricular reverse remodeling(LVRR)between coarctation of aorta(CoA)complicated by bicuspid aortic valve(BAV)and that by tricuspid aortic valve(TAV)after percutaneous intervention.Methods The clinical data on 47 patients undergoing percutaneous balloon dila-tion and stent implantation due to CoA in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2014 to December 2021 were retrospectively analyzed.According to the preoperative imaging data,there were 18 patients with BAVA and 29 with TAV.The results of echocardiography before and one year after the procedure were compared.Results CoA Vmax,CoA PG,LVEDd,LVEDdi,LVM and LVMI were significantly improved in CoA patients one year after percutaneous intervention,and 23.4%of the patients developed left ventricular reverse remodeling.AV Vmax,AV PG and LVEDdi in the patients with BAV were higher than those in the TAV group(P = 0.005 and P = 0.007;P = 0.03),and the rate of left ventricular reverse remodeling in BAV patients was lower than that in TAV patients,but there was no statistical significance.Multivariate analysis did not find any influence factors affecting left ventricular reverse remodeling one year after the procedure.Conclusions Part of the CoA patients develops left ventricular remodeling reversal one year after percutaneous intervention.LVRR in patients with BAV is lower than that in those with TAV,which still needs further clinical research.

Objective:To investigate the molecular biological mechanism of Bw07 allele and its transferase alteration carried by a proband of ABw07 subtype.Methods:A 2-year-old male child was selected as the research object. The peripheral blood of the proband and his parents was identified for ABO blood type by the test tube method, and the ABO subgroup PCR-SSP detection and ABO gene sequencing were performed on the three individuals to determine their blood type genotypes. Finally, the effect of the p.Arg352Gln mutation on Bw07 transferase was verified by virtual mutation, DUET structure prediction, molecular dynamics analysis, and in vitro cellular experiments.Results:The serological phenotypes of the proband and his mother were ABw and Bw, respectively, while his father was normal A. The ABO subgroup PCR-SSP assay identified the three genotypes as Bw07/A, Bw07/O, and A/A, respectively.Sanger sequencing further verified that the proband and his mother carried the Bw07 gene, and virtual mutation showed that the intermolecular forces were weakened by the R352Q mutation. DUET predicted that this p.Arg352Gln mutation could affect the thermodynamic stability of Bw07 transferase. Molecular dynamics analysis confirmed that the alteration of thermodynamic stability was mainly related to the appearance of large fluctuations in the amino acid backbone atoms in the 125-133, 193-198 and 336-354 regions, and in vitro cellular experiments further verified the weakened antigen synthesis of Bw07 transferase.Conclusion:The formation of the ABw07 phenotype is associated with the mutation of the highly conserved Arg352 to Gln in Bw07 transferase.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Background/Aims: We aimed to investigate the role and working mechanism of Homo sapiens circular RNA_0003602 (hsa_circ_0003602) in colorectal cancer (CRC) development. Methods: The expression of circ_0003602, miR-149-5p, and solute carrier family 38 member 1(SLC38A1) was detected by quantitative real-time polymerase chain reaction. RNase R assays were conducted to determine the characteristics of circ_0003602. CCK-8 assays, flow cytometry analysis, transwell invasion assays, wound healing assays and tube formation assays were employed to evaluate cell viability, apoptosis, invasion, migration, and angiogenesis. All protein levels were examined by Western blot or immunohistochemistry assay. The glutamine metabo-lism was monitored by corresponding glutamine, α-ketoglutarate and glutamate assay kits. Dual-luciferase reporter assay was utilized to confirm the targeted combination between miR-149-5p and circ_0003602 or SLC38A1. A xenograft tumor model was established to analyze the role of circ_0003602 in CRC tumor growth in vivo. Results: Circ_0003602 was upregulated in CRC tissues and cell lines. Circ_0003602 silencing suppressed CRC cell viability, migration, invasion, angiogenesis, and glutaminolysis; induced cell apoptosis in vitro; and blocked tumor growth in vivo. Moreover, circ_0003602 directly interacted with miR-149-5p to negatively regulate its expression, and circ_0003602 knockdown suppressed the malignant behaviors of CRC cells largely by upregulating miR-149-5p. MiR-149-5p directly bound to the 3’ untranslated region of SLC38A1 to induce its degradation, and miR-149-5p overexpression reduced the malignant potential of CRC cells largely by downregulating SLC38A1. Circ_0003602 positively regulated SLC38A1 expression by sponging miR-149-5p in CRC cells. Conclusions Circ_0003602 knockdown impedes CRC development by targeting the miR-149-5p/SLC38A1 axis, which provides a novel theoretical basis and new insights for CRC treatment.

Objective:To evaluate the clinical outcome of Robot-assisted sacroiliac screw fixation in the treatment of fragility fracture of the sacrum in the elderly.Methods:From March 2016 to June 2022, a retrospective analysis was performed on 30 patients with fragility fractures of the sacrum in the elderly who accepted robot-assisted sacroiliac screw to treat fragility fractures of the sacrum in our hospital. There were 12 males and 18 females with average age 71.03±8.25 years (range, 60-89 years). According to the classification of fragility fractures of the pelvis (FFP) in the elderly, there were 22 patients with FFP II, 2 patients with FFP III, and 6 patients with FFP IV. Surgical planning was based on the average CT value of S 1 channel and whether there is a transsacral screw channel. Robot-assisted sacroiliac screw fixation was performed during surgery. The pain of pre-operation and post-operation was evaluated using the visual analogue scale (VAS), the position of sacroiliac screws was evaluated by Gras grading, and the degree of functional recovery after surgery was evaluated using the Majeed function score. Results:All 30 patients successfully completed the operation. The mean operation time was 27.00±6.68 min (range, 18-35 min), the mean fluoroscopy times were 27.13±5.16 (range, 18-34), and the mean blood loss was 30.53±6.61 ml (range, 23-38 ml). All patients were followed up, and the mean follow-up time was 19.03±7.8 months (range, 8-25 months). The VAS was 5(5, 6), 4(3, 4), 3(2, 3), 0(0, 1) points before surgery, 1 week, 2 months and 6 months after surgery, respectively, and the difference was statistically significant ( H=103.26, P<0.001). After the surgery of 2 months, 6 months and the last follow-up time, the Majeed function scores were 88(83, 90), 91(87, 92), 92(90, 93) points, respectively, and the difference was statistically significant ( H=19.59, P<0.001). Screw position was evaluated according to Gras grading at 3 days after surgery, including 28 cases of level I, 2 cases of level II, and no screw penetrated the cortical bone or entered the sacral canal or sacral foramen. No vascular or nerve injury occured during the operation. 28 patients with FFS met the fracture healing criteria, and the healing time was 4.54±1.57 months (range, 3-7 months). Two patients had bone nonunion, one of whom underwent anterior ring plate removal due to infection of the pelvic anterior wound, and one month later, pelvic CT scan revealed loosening of the sacroiliac screw; the other one is considered to be related to too early weight bearing. Conclusion:For fragility fractures of the sacrum in elderly, Robot-assisted sacroiliac screw is an effective minimally invasive treatment, with high accuracy of screw placement, effective pain reduction, improved fracture healing rate, and achieve the satisfactory clinical efficacy.

Glioma is the most common primary brain tumor in adults and is essentially a polygenic abnormal disease. Solute carrier family 7 member 11 (SLC7A11) is a core component of the cystine/glutamate transporter and its expression is regulated at the transcriptional and translational levels. SLC7A11 mediates glioma cells proliferation, invasion and chemoradiotherapy resistance through regulation of oxidative stress and ferroptosis. Deep study of SLC7A11 will provide new theoretical basis and therapeutic targets for the treatment of gliomas.

Objective:To explore the effects of the γ-aminobutyric acid(GABA) neurons and melanin-concentrating hormone (MCH) neurons of the nucleus accumbens (NAc)-lateral hypothalamic area (LHA) neural pathway on the rewarding feeding(palatable food sweat condensed milk) in the obesity rats.Methods:Total 142 male Wistar rats of SPF grade were divided into normal diet (ND) group ( n=68) and high-fat diet induced obesity (DIO) group ( n=74) according to the principle of body mass matching. The rats in the two groups were given normal diet and high-fat diet for 8 weeks. Eight weeks later, 6 DIO rats were randomly selected to observe the nerve projection from GABA neurons in NAc to MCH neurons in LHA by fluorogold retrograde tracing combined fluorescence immunohistochemistry. And the expressions of c-Fos and MCH in LHA after ingestion of sweet condensed milk(rewarding feeding) were observed by fluorescence immunohistochemistry (6 rats in each group). GABA receptor agonist Musimol or GABA receptor antagonist Bicuculine was microinjected into the nucleus of LHA to observe the effect of GABA on rewarding food intake in ND and DIO rats ( n=8 in each group), and the changes of rewarding food intake after blocking MCH signal ( n=8 in each group). SPSS 17.0 was used for statistical analysis, two-way ANOVA and post hoc Bonferroni test were used for comparison among multiple groups, and t-test was used for comparison between two groups. Results:After 8 weeks of high-fat diet modeling, the intake of delicious food in DIO rats was significantly higher than that in ND rats((12.52±2.29) mL, (7.45±1.23) mL, t=4.778, P<0.01) after satiety.The results of fluorogold retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons in NAc projected nerve fibers to neurons in LHA, and GABA A receptors in some neurons in LHA coexisted with MCH.The results of NAc-LHA pathway on delicious food intake showed that the interaction between rat group and drug intervention was significant( F=9.869, P<0.01). Simple effect analysis showed that the intake of delicious food after microinjection of Musimol into LHA nucleus of ND rats was significantly lower than that of microinjection normal saline ((4.25±1.38) mL, (7.29±1.49) mL, P<0.01), while the intake of delicious food after injection of Bicuculine was significantly higher than that of microinjection normal saline((10.72±2.11) mL, (7.29±1.49) mL, P<0.05). The intake of delicious food after microinjection of Musimol into LHA nucleus in DIO group was significantly lower than that of microinjection normal saline((3.51±1.77)mL, (13.68±2.95) mL, P<0.01), but there was no significant difference between microinjection Bicuculine and microinjection normal saline ((14.83±3.44) mL, (13.68±2.95) mL, P>0.05). The results of blocking MCH signal on delicious food intake showed that the interaction effect between SNAP-94847 and Bicuculine intervention was not significant ( F=1.468, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=15.880, P<0.01)and the main effect of Bicuculine intervention was significant ( F=6.930, P<0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of ND rats was significantly less than that of injection normal saline((4.78±1.72) mL, (7.63±2.77) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((6.24±2.18) mL, (4.78±1.72) mL, P>0.05). In the DIO rats, the interaction effect between SNAP-94847 and Bicuculine intervention was not significant( F=0.006, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=18.46, P<0.01) and the main effect of Bicuculine intervention was not significant ( F=2.059, P>0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of DIO rats was significantly lower than that of injection normal saline((6.89±2.11) mL, (12.19±4.36) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((8.72±2.26) mL, (6.89±2.11) mL, P>0.05). Conclusion:GABAergic signal in NAc can regulate the expression of MCH in neurons of LHA. In the DIO rats, the sensitivity of MCH neurons in LHA to satiety signal decreases and the hedonic feeding increases.

Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional (3-D) space. However, there is no available three-dimensional behavior capture system that focuses on rodents. Here, we present MouseVenue3D, an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents. We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module. Then, we validated this process in behavior recognition tasks, and showed that 3-D behavioral data achieved higher accuracy than 2-D data. Subsequently, MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse. Finally, we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice. Our findings reveal that subtle, spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.
Animals ; Behavior, Animal ; Brain/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Mice ; Neuroimaging ; Rodentia

Measuring eye movement is a fundamental approach in cognitive science as it provides a variety of insightful parameters that reflect brain states such as visual attention and emotions. Combining eye-tracking with multimodal neural recordings or manipulation techniques is beneficial for understanding the neural substrates of cognitive function. Many commercially-available and custom-built systems have been widely applied to awake, head-fixed small animals. However, the existing eye-tracking systems used in freely-moving animals are still limited in terms of their compatibility with other devices and of the algorithm used to detect eye movements. Here, we report a novel system that integrates a general-purpose, easily compatible eye-tracking hardware with a robust eye feature-detection algorithm. With ultra-light hardware and a detachable design, the system allows for more implants to be added to the animal's exposed head and has a precise synchronization module to coordinate with other neural implants. Moreover, we systematically compared the performance of existing commonly-used pupil-detection approaches, and demonstrated that the proposed adaptive pupil feature-detection algorithm allows the analysis of more complex and dynamic eye-tracking data in free-moving animals. Synchronized eye-tracking and electroencephalogram recordings, as well as algorithm validation under five noise conditions, suggested that our system is flexibly adaptable and can be combined with a wide range of neural manipulation and recording technologies.