GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

AIM:To compare the effect of AT TORBI 709M and Tecnis ZMT intraocular lenses on astigmatism correction in patients with corneal astigmatism at 3 mo after operation based on the standard astigmatism vector analysis.METHODS: This was a retrospective case-control study. The clinical data of 69 patients(69 eyes)with corneal astigmatism who underwent phacoemulsification and implantation of toric intraocular lens(IOL)from June 2021 to December 2021 in Day Surgery Center of Xi'an No.1 Hospital was analyzed. The patients were divided into two groups. In group one, 38 cases(38 eyes)were implanted with AT TORBI 709M, and 31 patients(31 eyes)with Tecnis ZMT in group two. The axial length, preoperative astigmatism and axis, and the degree of intraocular lens were recorded. The uncorrected distance visual acuity(UCDVA), best corrected distance visual acuity(BCDVA), diopter, residual astigmatism and axis were recorded preoperatively and at 1 wk, 1 and 3 mo postoperatively. The postoperative surgical indicators, including spherical equivalent(SE), target induced astigmatism vector(TIA), surgically induced astigmatism vector(SIA), magnitude of error(ME), absolute value of angle of error(|AE|), absolute value of difference vector(|DV|), correction index(CI), and index of success(IOS)were evaluated by the standard astigmatism vector analysis.RESULTS:Postoperative UCDVA and BCDVA were significantly improved(all P<0.001), and there were statistically significant differences compared to preoperative UCDVA and BCDVA(all P<0.001). While, there was no significant difference in UCDVA and BCDVA between the two groups(P=0.275, 0.124). The standard astigmatism vector analysis showed that a good astigmatism correction was achieved in both AT TORBI 709M group and Tecnis ZMT group, and both |DV| and IOS were close to 0(P=0.329, 0.288). The CI of the AT TORBI 709M group was closer to 1, indicating a better astigmatism correction, while the CI of the Tecnis ZMT group was higher than 1, suggesting an overcorrection of astigmatism. However, the difference between the two groups was not statistically significant(P=0.193). The mean residual astigmatism at 3 mo postoperatively was -0.11±0.91 D in the AT TORBI 709M group and -0.46±0.76 D in the Tecnis ZMT group, respectively, showing no statistically significance difference(t=1.732, P=0.088).CONCLUSION:Both the flat loop AT TORBI 709M and the double C-loop Tecnis ZMT intraocular lenses can effectively improve postoperative visual acuity in patients with regular corneal astigmatism, showing good rotational stability and comparable correction abilities for both astigmatism with the rule and against-the-rule astigmatism.

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

RNA modifications constitute a crucial class of post-transcriptional chemical alterations that profoundly influence RNA stability and translational efficiency, thereby shaping cellular protein expression profiles. These diverse chemical marks are ubiquitously involved in key biological processes, including cell proliferation, differentiation, apoptosis, and metastatic potential, and they exert precise regulatory control over these functions. A major advance in the field is the recognition that RNA modifications do not act in isolation. Instead, they participate in complex, dynamic interactions—through synergistic enhancement, antagonism, competitive binding, and functional crosstalk—forming what is now termed the “RNA modification interactome” or “RNA modification interaction network.” The formation and functional operation of this interactome rely on a multilayered regulatory framework orchestrated by RNA-modifying enzymes—commonly referred to as “writers,” “erasers,” and “readers.” These enzymes exhibit hierarchical organization within signaling cascades, often functioning in upstream-downstream sequences and converging at critical regulatory nodes. Their integration is further mediated through shared regulatory elements or the assembly into multi-enzyme complexes. This intricate enzymatic network directly governs and shapes the interdependent relationships among various RNA modifications. This review systematically elucidates the molecular mechanisms underlying both direct and indirect interactions between RNA modifications. Building upon this foundation, we introduce novel quantitative assessment frameworks and predictive disease models designed to leverage these interaction patterns. Importantly, studies across multiple disease contexts have identified core downstream signaling axes driven by specific constellations of interacting RNA modifications. These findings not only deepen our understanding of how RNA modification crosstalk contributes to disease initiation and progression, but also highlight its translational potential. This potential is exemplified by the discovery of diagnostic biomarkers based on interaction signatures and the development of therapeutic strategies targeting pathogenic modification networks. Together, these insights provide a conceptual framework for understanding the dynamic and multidimensional regulatory roles of RNA modifications in cellular systems. In conclusion, the emerging concept of RNA modification crosstalk reveals the extraordinary complexity of post-transcriptional regulation and opens new research avenues. It offers critical insights into the central question of how RNA-modifying enzymes achieve substrate specificity—determining which nucleotides within specific RNA transcripts are selectively modified during defined developmental or pathological stages. Decoding these specificity determinants, shaped in large part by the modification interactome, is essential for fully understanding the biological and pathological significance of the epitranscriptome.

Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.

With the increasing application of immune checkpoint inhibitors(ICI)in anti-tumor therapy,ICI related infections are often neglected.Mycobacterium tuberculosis(MTB)is also a common pathogen.We reported a case of ICI related pulmonary tuberculosis from Zhongshan Hospital,Fudan University.Meanwhile,18 cases of ICI related tuberculosis infection were collected through literature search,and the characteristics of ICI related tuberculosis were analyzed to improve the understanding in clinic practice.All the cases were confirmed TB including 15 cases of pulmonary tuberculosis(1 case with complication of intestinal tuberculosis)and 4 cases of extra-pulmonary tuberculosis(1 case of disseminated tuberculosis,bone tuberculosis,tuberculous pericarditis and tuberculous pleurisy,respectively).The chest CT characteristics of pulmonary tuberculosis mainly included centrilobular nodules,ground glass nodules,empty lesions,patchy shadows,consolidation and large infiltration.Eighteen cases started anti-tuberculosis treatment,while 4 cases continued ICI treatment.Three cases suspended ICI(2 cases had remission after reuse)and 11 cases stopped ICI,and 1 case was not mentioned.ICI related tuberculosis may be a direct complication of tumor immunotherapy.It is necessary to screen tuberculosis infection and exclude active tuberculosis before immunotherapy.If there are suspected symptoms such as fever,cough and sputum during ICI treatment,active tuberculosis should be taken into account.

Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P＜0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P＜0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)％of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)％.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)％of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)％.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

BACKGROUND:A large number of studies have investigated the effects of whole body vibration training at different frequencies on muscle strength,but less is reported on the differences in the efficacy of vibration training at different frequencies on patellar tendinopathy. OBJECTIVE:To explore the effect of eccentric training of quadriceps combined with different frequency of whole body vibration training on patellar tendinopathy. METHODS:From April to June 2022,48 patients with patellar tendinopathy were recruited from Wuhan Sports University and randomly divided into eccentric training group(n=12),30 Hz group(n=12),40 Hz group(n=12),and 50 Hz group(n=12).The eccentric training group only completed eccentric training of the quadriceps.The 30 Hz,40 Hz and 50 Hz groups performed the whole body vibration training with the amplitude of 2 mm and frequencies of 30 Hz,40 Hz and 50 Hz respectively on the basis of the eccentric training of the quadriceps.The intervention lasted for 8 weeks,three times a week.Before and after the intervention,the patients'surface electromyography signals of the quadriceps,kinematics and dynamics data of knee joint at the time of landing in deep jump and the time of peak vertical ground reaction,Visual Analogue Scale score,Victorian Institute of Sports Assessment-Patellar score were evaluated. RESULTS AND CONCLUSION:After 8 weeks of intervention,compared with the eccentric training group,the median frequency of the lateral and medial femoris muscles were significantly higher in the 40 Hz and 50 Hz groups(P＜0.05).At the time of landing,the knee joint flexion angle and external rotation moment in the 40 Hz and 50 Hz groups were significantly lower than those in the eccentric training group(P＜0.05),while the knee joint flexion angle in the 50 Hz group was significantly lower than that in the 30 Hz group(P＜0.05).At the peak moment of vertical ground reaction,the knee extension torque in the 40 Hz group was significantly lower than that in the eccectric training group(P＜0.05);the knee flexion angle and knee extension torque in the 50 Hz group were significantly lower than those in the eccentric training group(P＜0.05).The Visual Analogue Scale scores in the 50 Hz and 40 Hz groups were significantly lower than those in the eccentric training group(P＜0.05).The Victorian Institute of Sports Assessment-Patellar score in the 50 Hz group was significantly higher than that in the eccentric training group and 30 Hz group(P＜0.05).To conclude,eccentric training of the quadriceps combined with 50 Hz whole body vibration training can significantly improve quadriceps'strength,endurance and activation rate of the vastus lateralis muscle,reduce the pain of knee joint,and improve the function of the knee joint in patients with patellar tendinopathy.

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L^-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.