The impact of disc degeneration on the dynamic characteristics of the lumbar spine: a finite element analysis.

The dynamics of disc degeneration was analyzed to determine the effect of disc degeneration at the L4-L5 segment on the dynamic characteristics of the total lumbar spine. A three-dimensional nonlinear finite element model of the L1-S1 normal lumbar spine was constructed and validated. This normal model was then modified to construct two degeneration models with different degrees of degeneration (mild, moderate) at the L4-L5 level. Modal analysis, harmonic response analysis, and transient dynamics analysis were performed on the total lumbar spine when experiencing following compressive loading (500 N). As the degree of disc degeneration increased, the vibration patterns corresponding to the first three orders of the model's intrinsic frequency were basically unchanged, with the first order being in the left-right lateral bending direction, the second order being in the forward-flexion and backward-extension direction, and the third order being in the axial stretching direction. The nucleus pulposus pressure peaks corresponding to the first order intrinsic frequency for the harmonic response analysis are all on the right side of the model, with sizes of 0.053 MPa, 0.061 MPa, and 0.036 MPa, respectively; the nucleus pulposus pressure peaks corresponding to the second order intrinsic frequency are all at the rear of the model, with sizes of 0.13 MPa, 0.087 MPa, and 0.11 MPa, respectively; and the nucleus pulposus pressure peaks corresponding to the third order intrinsic frequency are all at the front of the model, with sizes of 0.19 MPa, 0.22 MPa, and 0.22 MPa, respectively. The results of the transient analysis indicated that over time, the response curves of the healthy model, the mild model, and the moderate model all exhibited cyclic response characteristics. Intervertebral disc degeneration did not adversely affect the vibration characteristics of the entire lumbar spine system. Intervertebral disc degeneration significantly altered the dynamics of the degenerative segments and their neighboring normal segments. The process of disc degeneration gradually shifted the load from the nucleus pulposus to the annulus fibrosus when the entire lumbar spine was subjected to the same vibratory environment.

Origin and dispersal history of Hepatitis B virus in Eastern Eurasia.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Severity of COVID-19 infection in patients with COVID-19 combined with diabetes.

PURPOSE: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. METHODS: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. RESULTS: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. CONCLUSION: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

New Carbon Materials for Multifunctional Soft Electronics.

Soft electronics are garnering significant attention due to their wide-ranging applications in artificial skin, health monitoring, human-machine interaction, artificial intelligence, and the Internet of Things. Various soft physical sensors such as mechanical sensors, temperature sensors, and humidity sensors are the fundamental building blocks for soft electronics. While the fast growth and widespread utilization of electronic devices have elevated life quality, the consequential electromagnetic interference (EMI) and radiation pose potential threats to device precision and human health. Another substantial concern pertains to overheating issues that occur during prolonged operation. Therefore, the design of multifunctional soft electronics exhibiting excellent capabilities in sensing, EMI shielding, and thermal management is of paramount importance. Because of the prominent advantages in chemical stability, electrical and thermal conductivity, and easy functionalization, new carbon materials including carbon nanotubes, graphene and its derivatives, graphdiyne, and sustainable natural-biomass-derived carbon are particularly promising candidates for multifunctional soft electronics. This review summarizes the latest advancements in multifunctional soft electronics based on new carbon materials across a range of performance aspects, mainly focusing on the structure or composite design, and fabrication method on the physical signals monitoring, EMI shielding, and thermal management. Furthermore, the device integration strategies and corresponding intriguing applications are highlighted. Finally, this review presents prospects aimed at overcoming current barriers and advancing the development of state-of-the-art multifunctional soft electronics.

Safety and effectiveness of the three-dimensional-printed guide plate-assisted rotation axis positioning of a hinged external fixator for the elbow.

PURPOSE: We aimed to evaluate the safety and effectiveness of three-dimensional (3D)-printed guide plates for assisting in the positioning of the rotation axis of an elbow-hinged external fixator. METHODS: Terrible triad (TT) patients, who were screened using the predefined inclusion and exclusion criteria, underwent installation of a hinged external fixator on the basis of internal fixation; 3D-printed guide plates, generated from the patient's imaging data, assisted in positioning the rotation axis. All patients received the same peri-operative management and were followed up at six, 12, 24, and 48 weeks postoperatively. The duration of positioning pin placement, the number of fluoroscopies, pin placement success rate, types and incidence of post-operative complications, and the Mayo elbow performance score (MEPS) of the diseased elbow and range of motion (ROM) of both elbows were assessed. RESULTS: In 25 patients who completed the follow-up, the average time required for positioning pin placement was 329.32 ± 42.38 s (263-443 s), the average number of fluoroscopies was 2.32 ± 0.48 times (2-3 times), and the pin placement success rate was 100%. At the last follow-up, the mean MEPS of the diseased elbow was 97.50 ± 6.92 (75-100), with an excellent and good rate of 100%, and all patients demonstrated stable concentric reduction. The average range of flexion and extension was 135.08° ± 17.10° (77-146°), while the average range of rotation was 169.21° ± 18.14° (108-180°). No significant difference was observed in the average ROM between the both elbows (P > 0.05). Eight (32%) patients developed post-operative complications, including elbow stiffness due to heterotopic ossification in three (12%) patients, all of whom did not require secondary intervention. CONCLUSION: Utilizing 3D-printed guide plates for positioning the rotation axis of an elbow-hinged external fixator significantly reduced intra-operative positioning pin placement time and the number of fluoroscopies with excellent positioning results. Satisfactory results were also obtained in terms of post-operative complications, elbow ROM, and functional scores.

Coaxial electrospun Ag-NPs-loaded endograft membrane with long-term antibacterial function treating mycotic aortic aneurysm.

The use of endovascular stent-graft has become an important option in the treatment of aortic pathologies. However, the currently used endograft membranes have limited ability to prevent bacterial colonization. This makes them unsuitable for the treatment of mycotic aneurysms, as the infection is prone to progress after endograft implantation. Moreover, even in non-mycotic aortic pathologies, endograft infections can occur in the short or long term, especially for patients with diabetes mellitus or in immune insufficiency conditions. So, this study aimed to develop a kind of Ag-NPs-loaded endograft membrane by coaxial electrospinning technique, and a series of physical and chemical properties and biological properties of the Ag-NPs-loaded membrane were characterized. Animal experiments conducted in pigs confirmed that the Ag-NPs-loaded membrane was basically non-toxic, exhibited good biocompatibility, and effectively prevented bacterial growth in a mycotic aortic aneurysm model. In conclusion, the Ag-NPs-loaded membrane exhibited good biocompatibility, good anti-infection function and slow-release of Ag-NPs for long-term bacteriostasis. Thus, the Ag-NPs-loaded membrane might hold potential for preventing infection progression and treating mycotic aortic aneurysms in an endovascular way.

RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination.

Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. However, the role of ubiquitination of these TFs during oligodendroglial development is yet unexplored. Here, we find that RNF220, a known leukodystrophy-related E3 ubiquitin ligase, is required for oligodendroglial development. RNF220 depletion in oligodendrocyte lineage cells impedes oligodendrocyte progenitor cell proliferation, differentiation, and (re)myelination, which consequently leads to learning and memory defects. Mechanistically, RNF220 targets Olig1/2 for K63-linked polyubiquitination and stabilization during oligodendroglial development. Furthermore, in a knock-in mouse model of leukodystrophy-related RNF220R365Q mutation, the ubiquitination and stabilization of Olig proteins are deregulated in oligodendroglial cells. This results in pathomimetic oligodendroglial developmental defects, impaired myelination, and abnormal behaviors. Together, our evidence provides an alternative insight into PTMs of oligodendroglial TFs and how this essential process may be implicated in the etiology of leukodystrophy.

Association between fatty liver index and controlled attenuation parameters as markers of metabolic dysfunction-associated fatty liver disease and bone mineral density: observational and two-sample Mendelian randomization studies.

Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE: Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS: Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS: After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION: No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.

Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers.

BACKGROUND: EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers. MATERIALS AND METHODS: The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study. RESULTS: After applied 15 g of the cream for 4 h to a 100 cm2 area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated. CONCLUSION: The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study. CLINICAL TRIAL REGISTRATION: CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.

A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma.

Bladder urothelial carcinoma (BLCA) is one of the most common cancer-related deaths in the world, along with high mortality. Due to the difficult detection of early symptoms, the treatment for this disease is still dissatisfactory. Thus, the current research hotspot is beginning to focus on the immune microenvironment in this disease, aiming to provide guidance for diagnosis and treatment. In this study, the single-cell RNA sequencing data downloaded from the gene expression omnibus database was used to classify the immune cells of BLCA. And the final seven T-cell-related cell clustering genes associated with BLCA prognosis (HSPA2, A2M, JUN, PDGFRB, GBP2, LGALS1, and GAS6) were screened out, and then used for constructing the prognostic model against BLCA based on the Cox and LASSO regression analysis. Satisfactorily, the model could efficiently evaluate the overall survival of BLCA and had the potential to be applied for the clinic treatment. Moreover, we also revealed that the difference in immune infiltration levels and gene mutation might account for the diverse prognosis in BLCA patients. In a word, our findings provided a novel insight for designing efficient immunotherapies for BLCA.

A tumor microenvironment-activatable nanoplatform with phycocyanin-assisted in-situ nanoagent generation for synergistic treatment of colorectal cancer.

The in-situ generation of therapeutic agents in targeted lesions is promising for revolutionizing oncotherapy but is limited by the low production efficiency. Given the specific tumor microenvironment (TME) of colorectal cancer (CRC), i.e., mild acidity, overexpressed H2O2, glutathione (GSH) and H2S, we develop phycocyanin (PC) encapsulated PZTC/SS/HA nanocapsules (NCs) for TME-responsive, protein-assisted "turn-on'' therapy of CRC. The NCs are prepared by sequentially assembling Cu2+-tannic acid (TA) coordination shell, disulfide bond-bearing cross-linker, and hyaluronic acid (HA) on the sacrificial template ZIF-8, thus achieving pH-, GSH-responsiveness, and tumor targeting capability, respectively. Once reaching the CRC sites, the NCs can quickly disintegrate and release Cu2+ and PC, accompanied by subsequent endogenous H2S-triggered generation of copper sulfide (CuS). Significantly, the intracellular sulfidation process can be accelerated by PC, thereby enabling efficient photothermal therapy (PTT) under NIR-Ⅱ laser. Besides, Cu2+-associated chemodynamic therapy (CDT) can be simultaneously activated and enhanced by PTT-induced local hyperthermia and disulfide bond-induced GSH consumption. This CRC-targeted and TME-activated synergistic PTT/CDT strategy displays high therapeutic efficacy both in vitro and in vivo, which can open up a new avenue for biomolecule-assisted in-situ nanoagent generation and effective TME-responsive synergistic treatment of CRC.

Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma.

Sonic hedgehog (Shh)-group medulloblastoma (MB) (Shh-MB) encompasses a clinically and molecularly distinct group of cancers originating from the developing nervous system with aberrant high Shh signaling as a causative driver. We recently reported that RNF220 is required for sustained high Shh signaling during Shh-MB progression; however, how high RNF220 expression is achieved in Shh-MB is still unclear. In this study, we found that the ubiquitin E3 ligases Smurf1 and Smurf2 interact with RNF220, and target it for polyubiquitination and degradation. In MB cells, knockdown or overexpression of Smurf1 or Smurf2 promotes or inhibits cell proliferation, colony formation and xenograft growth, respectively, by controlling RNF220 protein levels, and thus modulating Shh signaling. Furthermore, in clinical human MB samples, the protein levels of Smurf1 or Smurf2 were negatively correlated with those of RNF220 or GAB1, a Shh-MB marker. Overall, this study highlights the importance of the Smurf1- and Smurf2-RNF220 axes during the pathogenesis of Shh-MB and provides new therapeutic targets for Shh-MB treatment.

Cooperative operation strategy of electric vehicle and photovoltaic power station considering carbon reduction benefit under dynamic electricity price.

In the context of the global green and low-carbon transformation, microgrids containing renewable energy have been widely developed. At present, renewable energy generation has the disadvantages of instability and low energy density. In addition, the high proportion of electric vehicles (EVs) connected to the state grid will cause different degrees of disturbance to its safe operation. Therefore, a coordinated operation strategy of EV and photovoltaic (PV)-energy-storage charging stations induced by dynamic electricity price considering carbon reduction benefit is proposed. On the power generation side, a dual-axis PV tracking control method with "fixed frequency + variable frequency" control is proposed. One day is used as a period to divide the time segments, and the same time segment uses the fixed frequency tracking method, while different time segments use the variable frequency tracking method to improve the power generation efficiency. On the electricity consumption side, a dynamic electricity price strategy is adopted, using the minimum carbon reduction cost as the reward function, optimizing the dynamic electricity price under the minimum carbon reduction cost using the deep deterministic policy gradient (DDPG) algorithm to promote the shifting of EV charging load to the effective hours of PV generation. In conclusion, the simulation analysis is carried out in Zibo City, and the generation capacity of the proposed tracking method on the power generation side is improved by about 32% compared with the fixed PV generation capacity. Compared with the time-of-use electricity price, the optimized dynamic electricity price under the minimum carbon reduction cost can better promote the load transfer and photoelectric consumption of EVs and reduce the carbon reduction cost.

A multidisciplinary study on the social customs of the Tang Empire in the Medieval Ages.

Multidisciplinary research on human remains can provide important information about population dynamics, culture diffusion, as well as social organization and customs in history. In this study, multidisciplinary analyses were undertaken on a joint burial (M56) in the Shuangzhao cemetery of the Tang Dynasty (618-907 AD), one of the most prosperous dynasties in Chinese history, to shed light on the genetic profile and sociocultural aspects of this dynasty. The archaeological investigation suggested that this burial belonged to the Mid-Tang period and was used by common civilians. The osteological analysis identified the sex, age, and health status of the three individuals excavated from M56, who shared a similar diet inferred from the stable isotopic data. Genomic evidence revealed that these co-buried individuals had no genetic kinship but all belonged to the gene pool of the ancient populations in the Central Plains, represented by Yangshao and Longshan individuals, etc. Multiple lines of evidence, including archaeology, historic records, as well as chemical and genetic analyses, have indicated a very probable familial joint burial of husband and wives. Our study provides insights into the burial customs and social organization of the Tang Dynasty and reconstructs a scenario of civilian life in historic China.

The Application of Multiple Magnetic Resonance Scanning Techniques in Evaluating the Stability of Intracranial Aneurysms.

Purpose: To evaluate the stability of unruptured intracranial aneurysm (UIA) with high-resolution magnetic resonance imaging of the vessel wall (HR-VWI). Materials and Methods: A total of 92 UIA patients were enrolled. After MRA, HR-VWI imaging, the reconstruction of volume rendering (VR) and maximum intensity projection (MIP) were performed to observe the location and size of aneurysms, AR value (ratio of aneurysm height to aneurysmal diameter), SR value (ratio of maximum tumor depth to proximal parent artery diameter), and signal intensity were measured. Results: There were 7 aneurysms with UIA located in the anterior cerebral artery, 31 aneurysms with UIA in the middle cerebral artery, 1 aneurysm with UIA in the posterior cerebral artery, 18 aneurysms with UIA in the anterior communication, 5 aneurysms with UIA in the posterior communication, 34 aneurysms with UIA in the intracranial segment of the internal carotid artery and 3 aneurysms with UIA in the vertebral artery. Among them, 8 patients had more than two multiple aneurysms. The lesion size was 2-38mm (6.3 ± 5.09). There are 46 aneurysms with wall enhancement: the maximum SR value was 7.03 and the minimum 1.2, and the maximum AR value was 7.5 and the minimum 1.0. Fifty-five aneurysms showed no enhancement of the tumor wall. The maximum SR value was 4.55 and the minimum 0.58, and the maximum AR value was 4.0 and the minimum 0.6, respectively. Patients were divided into a stable group and an unstable group according to the aneurysm wall. The enhancement rate, SR value, and AR value in the stable aneurysm group were significantly lower than those in the unstable aneurysm group (P < 0.05). Conclusion: MRA and HR-VWI can objectively reflect the stability of aneurysms by judging the morphology, SR value, and signal enhancement of UIA, and can provide a certain basis for diagnosis and treatment, which has become routine examination.

Noninvasive evaluation of PD-L1 expression in non-small cell lung cancer by immunoPET imaging using an acylating agent-modified antibody fragment.

PURPOSE: The aim of this study was to explore an effective 124I labeling strategy and improve the signal-to-noise ratio when evaluating the expression of PD-L1 using an 124I-iodinated durvalumab (durva) F(ab')2 fragment. METHODS: The prepared durva F(ab')2 fragments were incubated with N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP); after purification, the HPP-durva F(ab')2 was iodinated using Iodo-Gen method. After the radiochemical purity, stability, and specific activities were determined, the binding affinities of probes prepared using different labeling strategies were compared in vitro. The clinical application value of [124I]I-HPP-durva-F(ab')2 was confirmed by PET imaging. To more objectively evaluate the in vivo distribution and clearance of tracers, the pharmacokinetics and biodistribution assays were also performed. RESULTS: After being modified with SHPP, the average conjugation number of SHPP per durva-F(ab')2 identified by LC-MS was about 8.92 ± 2.84. The prepared [124I]I-HPP-durva F(ab')2 was obtained with a satisfactory radiochemical purity of more than 98% and stability of more than 93% when incubated for 72 h. Compared with unmodified [124I]I-durva F(ab')2, the specific activity of [124I]I-HPP-durva-F(ab')2 was improved (52.91 ± 5.55 MBq/mg and 15.91 ± 0.74 MBq/mg), while the affinity did not significantly change. The biodistribution experiments and PET imaging showed that the prepared [124I]I-HPP-durva-F(ab')2 exhibited an accelerated clearance and improved tumor-to-background ratio compared with [124I]I-durva-F(ab')2. The specificity of [124I]I-HPP-durva-F(ab')2 to PD-L1 was well demonstrated both in vitro and in vivo. CONCLUSIONS: A PD-L1 PET imaging probe [124I]I-HPP-durva F(ab')2 was successfully synthesized through the SHPP modification strategy. The prepared probe was able to accurately evaluate the PD-L1 expression level through high-contrast noninvasive imaging.

Solving the two-decades-old murder case through joint application of ZooMS and ancient DNA approaches.

Bones are one of the most common biological types of evidence in forensic cases. Discriminating human bones from irrelevant species is important for the identification of victims; however, the highly degraded bones could be undiagnostic morphologically and difficult to analyze with standard DNA profiling approaches. The same challenge also exists in archaeological studies. Here, we present an initial study of an analytical strategy that involves zooarchaeology by mass spectrometry (ZooMS) and ancient DNA methods. Through the combined strategy, we managed to identify the only biological evidence of a two-decades-old murder case - a small piece of human bone out of 19 bone fragments - and confirmed the kinship between the victim and the putative parents through joint application of next-generation sequencing (NGS) and Sanger sequencing methods. ZooMS effectively screened out the target human bone while ancient DNA methods improve the DNA yields. The combined strategy in this case outperforms the standard DNA profiling approach with shorter time, less cost, as well as higher reliability for the genetic identification results. HIGHLIGHTS: • The first application of zooarchaeology by mass spectrometry technique in the forensic case for screening out human bones from bone fragment mixtures. • Application of ancient DNA technique to recover the highly degraded DNA sequence from the challenging sample that failed standard DNA profiling approaches. • A fast, sensitive, and low-cost strategy that combines the strengths of protein analysis and DNA analysis for kinship identification in forensic research.

Enzymatic biosensor based on dendritic gold nanostructure and enzyme precipitation coating for glucose sensing and detection.

With the development of blood glucose monitoring medical devices, higher requirements are put forward for the sensitivity and detection limit of biosensors. Herein, a high-performance flexible enzymatic glucose biosensor was prepared by electrochemical deposition of dendritic gold nanostructure on carbon cloth substrate, then covalently immobilizing glucose oxidase on the dendritic gold, and then increasing enzyme loading by enzyme precipitation coating. The morphology of dendritic gold nanostructures was characterized by scanning electron microscopy (SEM). The electrochemical performance of the biosensor was analyzed by cyclic voltammetry (CV), chronoamperometry curve and electrochemical impedance spectroscopy (EIS). It is found that the obtained biosensor has high sensitivity (72.45 µA mM-1 cm-2), low detection limit (6.7 µM) and ultra-wide linear range (0.02-31.7 mM) for glucose detection. In addition, the biosensor also has good selectivity, reproducibility and stability. In the detection of real serum samples, the biosensor also shows good accuracy and practicality. The results show that the new biosensor has great potential for applications in biomedical and health care.