Spray-lithography of hybrid graphene-perovskite paper-based photodetectors for sustainable electronics.

Paper is an ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems. When combined with nanomaterial-based devices, it can be harnessed for various Internet-of-Things applications, ranging from wearable electronics to smart packaging. However, paper remains a challenging substrate for electronics due to its rough and porous nature. In addition, the absence of established fabrication methods is impeding its utilization in wearable applications. Unlike other paper-based electronics with added layers, in this study, we present a scalable spray-lithography on a commercial paper substrate. We present a non-vacuum spray-lithography of chemical vapor deposition (CVD) single-layer graphene (SLG), carbon nanotubes (CNTs), and perovskite quantum dots (QDs) on a paper substrate. This approach combines the advantages of two large-area techniques: CVD and spray-coating. The first technique allows for the growth of SLG, while the second enables the spray coating of a mask to pattern CVD SLG, electrodes (CNTs), and photoactive (QDs) layers. We harnessed the advantages of perovskite QDs in photodetection, leveraging their strong absorption coefficients. Integrating them with the graphene enhanced the photoconductive gain mechanism, leading to high external responsivity. The presented device shows high external responsivity of ~520A/W at 405nm at <1V bias due to photoconductive gain mechanism. The prepared paper-based photodetectors (PDs) achieved an external responsivity of 520 A/W under 405 nm illumination at <1V operating voltage. To the best of our knowledge, our devices have the highest external responsivity amongst paper-based PDs. By fabricating arrays of PDs on a paper substrate in the air, this work highlights the potential of this scalable approach for enabling ubiquitous electronics on paper.

Crosstalk between autophagy and ferroptosis mediate injury in ischemic stroke by generating reactive oxygen species.

Stroke represents a significant threat to global human health, characterized by high rates of morbidity, disability, and mortality. Predominantly, strokes are ischemic in nature. Ischemic stroke (IS) is influenced by various cell death pathways, notably autophagy and ferroptosis. Recent studies have increasingly highlighted the interplay between autophagy and ferroptosis, a process likely driven by the accumulation of reactive oxygen species (ROS). Post-IS, either the inhibition of autophagy or its excessive activation can escalate ROS levels. Concurrently, the interaction between ROS and lipids during ferroptosis further augments ROS accumulation. Elevated ROS levels can provoke endoplasmic reticulum stress-induced autophagy and, in conjunction with free iron (Fe2+), can trigger ferroptosis. Moreover, ROS contribute to protein and lipid oxidation, endothelial dysfunction, and an inflammatory response, all of which mediate secondary brain injury following IS. This review succinctly explores the mechanisms of ROS-mediated crosstalk between autophagy and ferroptosis and the detrimental impact of increased ROS on IS. It also offers novel perspectives for IS treatment strategies.

Cowhide gelatin peptide as a source of antioxidants for inhibiting the deterioration of pudding quality during storage.

To investigate the effect of gelatin peptide on the inhibition of quality deterioration in stored pudding, gelatin peptide with antioxidant properties was added to pudding products. For this purpose, a pudding recipe containing gelatin peptides was created. The gelatin peptides were characterized based on their antioxidant activity and protein structure. It was found that gelatin peptides had better antioxidant properties, lower thermal stability and crystallinity, higher hydrophobic amino acid content, and greater surface hydrogen bond exposure than commercially available peptides. Properties such as the pH, colony growth, and sensory characteristics of the pudding were characterized at 4 °C and 25 °C. The results showed that the addition of 0.5-1.0 % gelatin peptide to pudding was capable of significantly (P< 0.05) slowing down the decline in pH and sensory scores of the pudding and significantly inhibiting colony growth. It could prolong its storage life by five days at 4 °C and three days at 25 °C.

Vacuum Evaporation Plating Enabling ≤ 10 µm Ultrathin Lithium Foils for Lithium Metal Batteries.

Lithium (Li) metal is widely recognized as a viable candidate for anode material in future battery technologies due to its exceptional energy density. Nevertheless, the commercial Li foils in common use are too thick (≈100 µm), resulting in a waste of Li resources. Herein, by applying the vacuum evaporation plating technology, the ultra-thin Li foils (VELi) with high purity, strong adhesion, and thickness of less than 10 µm are successfully prepared. The manipulation of evaporation temperature allows for convenient regulation of the thickness of the fabricated Li film. This physical thinning method allows for fast, continuous, and highly accurate mass production. With a current density of 0.5 mA cm-2 for a plating amount of 0.5 mAh cm-2, VELi||VELi cells can stably cycle for 200 h. The maximum utilization of Li is already more than 25%. Furthermore, LiFePO4||VELi full cells present excellent cycling performance at 1 C (1 C = 155 mAh g-1) with a capacity retention rate of 90.56% after 240 cycles. VELi increases the utilization of active Li and significantly reduces the cost of Li usage while ensuring anode cycling and multiplication performance. Vacuum evaporation plating technology provides a feasible strategy for the practical application of ultra-thin Li anodes.

Mechanisms of intermittent theta-burst stimulation attenuating nerve injury after ischemic reperfusion in rats through endoplasmic reticulum stress and ferroptosis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) exerts neuroprotective effects early in cerebral ischemia/reperfusion (I/R) injury. Intermittent theta-brust stimulation (iTBS), a more time-efficient modality of rTMS, improves the efficiency without at least decreasing the efficacy of the therapy. iTBS elevates cortical excitability, and in recent years it has become increasingly common to apply iTBS to patients in the early post-IS period. However, little is known about the neuroprotective mechanisms of iTBS. Endoplasmic reticulum stress (ERS), and ferroptosis have been shown to be involved in the development of I/R injury. We aimed to investigate the potential regulatory mechanisms by which iTBS attenuates neurological injury after I/R in rats. METHODS: Rats were randomly divided into three groups: sham-operated group, MCAO/R group, and MCAO/R + iTBS group, and were stimulated with iTBS 36 h after undergoing middle cerebral artery occlusion (MCAO) or sham-operated. The expression of ERS, ferroptosis, and apoptosis-related markers was subsequently detected by western blot assays. We also investigated the mechanism by which iTBS attenuates nerve injury after ischemic reperfusion in rats by using the modified Neurological Severity Score (mNSS) and the balance beam test to measure nerve function. RESULTS: iTBS performed early in I/R injury attenuated the levels of ERS, ferroptosis, and apoptosis, and improved neurological function, including mNSS and balance beam experiments. It is suggested that this mode of stimulation reduces the cost per treatment by several times without compromising the efficacy of the treatment and could be a practical and less costly intervention.

Resistance, mechanism, and fitness cost of specific bacteriophages for Pseudomonas aeruginosa.

The bacteriophage is an effective adjunct to existing antibiotic therapy; however, in the course of bacteriophage therapy, host bacteria will develop resistance to bacteriophages, thus affecting the efficacy. Therefore, it is important to describe how bacteria evade bacteriophage attack and the consequences of the biological changes that accompany the development of bacteriophage resistance before the bacteriophage is applied. The specific bacteriophage vB3530 of Pseudomonas aeruginosa (P. aeruginosa) has stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. Ten bacteriophage-resistant strains (TL3780-R) were induced using the secondary infection approach, and the plaque assay showed that vB3530 was less sensitive to TL3780-R. Identification of bacteriophage adsorption receptors showed that the bacterial surface polysaccharide was probably the adsorption receptor of vB3530. In contrast to the TL3780 parental strain, TL3780-R is characterized by the absence of long lipopolysaccharide chains, which may be caused by base insertion of wzy or deletion of galU. It is also intriguing to observe that, in comparison to the parent strain, the bacteriophage-resistant strains TL3780-R mostly exhibited a large cost of fitness (growth rate, biofilm formation, motility, and ability to produce enhanced pyocyanin). In addition, TL3780-R9 showed increased susceptibility to aminoglycosides and chlorhexidine, which may be connected to the loss and down-regulation of mexX expression. Consequently, these findings fully depicted the resistance mechanism of P. aeruginosa to vB3530 and the fitness cost of bacteriophage resistance, laying a foundation for further application of bacteriophage therapy.IMPORTANCEThe bacteriophage is an effective adjunct to existing antibiotic therapy; However, bacteria also develop defensive mechanisms against bacteriophage attack. Thus, there is an urgent need to deeply understand the resistance mechanism of bacteria to bacteriophages and the fitness cost of bacteriophage resistance so as to lay the foundation for subsequent application of the phage. In this study, a specific bacteriophage vB3530 of P. aeruginosa had stable biological characteristics, short incubation period, strong in vitro cleavage ability, and absence of virulence or resistance genes. In addition, we found that P. aeruginosa may lead to phage resistance due to the deletion of galU and the base insertion of wzy, involved in the synthesis of lipopolysaccharides. Simultaneously, we showed the association with the biological state of the bacteria after bacteria acquire bacteriophage resistance, which is extremely relevant to guide the future application of therapeutic bacteriophages.

CACNA1B protects naked mole-rat hippocampal neuron from apoptosis via altering the subcellular localization of Nrf2 after 60Co irradiation.

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation-induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next-generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation-induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

Tigecycline-Rifampicin Restrains Resistance Development in Carbapenem-Resistant Klebsiella pneumoniae.

The goal of this study was to clarify the synergistic antibacterial activity of the combination of tigecycline (TGC) and rifampicin (RIF). Additionally, the study sought to investigate the impact of this combination on the development of mutational resistance and to assess its efficacy in an in vivo model using Galleria mellonella. Through a checkerboard test, we found that the combination of TGC and RIF showed synergistic antibacterial activity against carbapenem-resistant Klebsiella pneumoniae (CRKP). The fractional inhibition concentration index (FICI) was found to be ≤0.5, confirming the potency of the combination. Additionally, this synergistic effect was further validated in vivo using the G. mellonella infection model. TGC-RIF treatment had a lower mutant prevention concentration (MPC) than that of monotherapy, indicating its potential to reduce the development of mutational resistance. We observed a substantial variation in the MPCs of TGC and RIF when they were measured at different proportions in the combinations. Furthermore, during the resistant mutant selection window (MSW) test, we noticed a correlation between strains with low FICI and low MSW. The expression of efflux-pump-related genes, namely rarA and acrB, is significantly decreased in the combination therapy group. This indicates that altered expression levels of certain efflux pump regulator genes are associated with a combined decrease in bacterial mutation resistance. In conclusion, the combination of TGC and RIF effectively suppresses antibiotic resistance selection in CRKP. This study establishes a paradigm for evaluating drug-resistant mutant suppression in antimicrobial combination therapy.

Study of Combined Effect of Bacteriophage vB3530 and Chlorhexidine on the Inactivation of Pseudomonas aeruginosa.

BACKGROUND: Chlorhexidine (CHG) is a disinfectant commonly used in hospitals. However, it has been reported that the excessive use of CHG can cause resistance in bacteria to this agent and even to other clinical antibiotics. Therefore, new methods are needed to alleviate the development of CHG tolerance and reduce its dosage. This study aimed to explore the synergistic effects of CHG in combination with bacteriophage against CHG-tolerant Pseudomonas aeruginosa (P. aeruginosa) and provide ideas for optimizing disinfection strategies in clinical environments as well as for the efficient use of disinfectants. METHODS: The CHG-tolerant P. aeruginosa strains were isolated from the First Affiliated Hospital of Wenzhou Medical University in China. The bacteriophage vB3530 was isolated from the sewage inlet of the hospital, and its genome was sequenced. Time-killing curve was used to determine the antibacterial effects of vB3530 and chlorohexidine gluconate (CHG). The phage sensitivity to 16 CHG-tolerant P. aeruginosa strains and PAO1 strain was detected using plaque assay. The emergence rate of resistant bacterial strains was detected to determine the development of phage-resistant and CHG-tolerant strains. Finally, the disinfection effects of the disinfectant and phage combination on the surface of the medical devices were preliminarily evaluated. RESULTS: The results showed that (1) CHG combined with bacteriophage vB3530 significantly inhibited the growth of CHG-resistant P. aeruginosa and reduced the bacterial colony forming units (CFUs) after 24 h. (2) The combination of CHG and bacteriophage inhibited the emergence of phage-resistant and CHG-tolerant strains. (3) The combination of CHG and bacteriophage significantly reduced the bacterial load on the surface of medical devices. CONCLUSIONS: In this study, the combination of bacteriophage vB3530 and CHG presented a combined inactivation effect to CHG-tolerant P. aeruginosa and reduced the emergence of strains resistant to CHG and phage. This study demonstrated the potential of bacteriophage as adjuvants to traditional disinfectants. The use of bacteriophage in combination with commercial disinfectants might be a promising method for controlling the spread of bacteria in hospitals.

Prevalence and clinical correlations of SF3B1 variants in lactotroph tumours.

OBJECTIVE: A somatic mutational hotspot in the SF3B1 gene was reported in lactotroph tumours. The aim of our study was to examine the prevalence of driver SF3B1 variants in a multicentre independent cohort of patients with lactotroph tumours and correlate with clinical data. DESIGN AND METHODS: This was a retrospective, multicentre study involving 282 patients with lactotroph tumours (including 6 metastatic lactotroph tumours) from 8 European centres. We screened SF3B1 exon 14 hotspot for somatic variants using Sanger sequencing and correlated with clinicopathological data. RESULTS: We detected SF3B1 variants in seven patients with lactotroph tumours: c.1874G > A (p.Arg625His) (n = 4, 3 of which metastatic) and a previously undescribed in pituitary tumours variant c.1873C > T (p.Arg625Cys) (n = 3 aggressive pituitary tumours). In two metastatic lactotroph tumours with tissue available, the variant was detected in both primary tumour and metastasis. The overall prevalence of likely pathogenic SF3B1 variants in lactotroph tumours was 2.5%, but when we considered only metastatic cases, it reached the 50%. SF3B1 variants correlated with significantly larger tumour size; higher Ki67 proliferation index; multiple treatments, including radiotherapy and chemotherapy; increased disease-specific death; and shorter postoperative survival. CONCLUSIONS: SF3B1 variants are uncommon in lactotroph tumours but may be frequent in metastatic lactotroph tumours. When present, they associate with aggressive tumour behaviour and worse clinical outcome.

Intraventricular SEEG and laser ablation for the treatment of infantile spasm: Technical note.

OBJECTIVES: Infantile spasm (IS) is an epileptic encephalopathy with ongoing neurological damage due to seizures and epileptiform abnormalities. Epilepsy surgery is considered for children refractory to drug therapy, especially when there is a focal brain lesion. In this study, we investigated the feasibility and efficacy of intraventricular stereotactic electroencephalography (SEEG) and laser ablation for the treatment of IS children with focal brain lesions. METHODS: We performed the first reported study using ventriculoscopic laser ablation to treat IS. Seven IS children with drug-resistant epilepsy and definite encephalomalacia on brain magnetic resonance imaging scan were included in this study. Ablation was performed after confirmation of epileptiform discharges by SEEG under the surveillance of ventriculoscope. RESULTS: The median follow-up time for the cohort was 3.1 years and 86% (6/7) of the children had an Engel class ≤III epilepsy at the final follow-up. Five (71%) children had a reduction in seizure medication usage, and the other two were on the same amount as preablation. None of the children experienced serious new neurological deficits. Laser ablation might result in seizure freedom by destroying the local brain network and blocking the spread of abnormal discharges. CONCLUSIONS: Intraventricular SEEG and laser ablation was feasible and effective for the treatment of IS. Further studies are warranted.

Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes.

OBJECTIVES: Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. METHODS: We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter - former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. RESULTS: During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, -96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. CONCLUSIONS: Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes.

Ureterocele with duplex collecting systems and febrile urinary tract infection risk.

PURPOSE: Ureterocele has been hypothesized to be the risk factor for febrile urinary tract infections (F-UTIs) in patients with duplex collecting systems, but this has not been proved, and our goal was to assess the relation between ureterocele with duplex collecting systems and F-UTIs. METHODS: We included individual-participant data from patients seen for complicated duplex collecting systems from 2010 to 2020 retrospectively followed. Those with using continuous low-dose antibiotic prophylaxis and incompletely duplicated systems were removed from the study. The participants were divided into two cohorts according to patients with or without ureterocele. The primary endpoint of this study was recurrent F-UTIs. RESULTS: We analyzed medical reports of 300 patients, of which 75% were female. Among the 300 patients, F-UTIs developed in 111/159 (69.8%) patients in the ureterocele group and in 69/141 (48.9%) patients in the no-ureterocele group. Univariate analysis found no discernible difference except in grade of hydronephrosis between ureterocele group and no-ureterocele group. Moreover, Cox proportional regression analysis revealed that patients of duplex system ureterocele might be intrinsically more prone to develop F-UTIs (adjusted hazard ratio 1.894; 95% CI 1.412-2.542; p  <  0.001). CONCLUSION: Among participants with duplex systems, the risk of recurrent F-UTIs in patients with ureterocele was higher than patients without it, and mini-invasive surgical correction should be considered at young age to reduce F-UTIs.

Associations Between Frailty and the Increased Risk of Adverse Outcomes Among 38,950 UK Biobank Participants With Prediabetes: Prospective Cohort Study.

BACKGROUND: Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. OBJECTIVE: We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. METHODS: We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. RESULTS: At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Robust results were generally observed in sensitivity analyses. CONCLUSIONS: In UK Biobank participants with prediabetes, both prefrailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden.

High-Order Correlation-Guided Slide-Level Histology Retrieval With Self-Supervised Hashing.

Histopathological Whole Slide Images (WSIs) play a crucial role in cancer diagnosis. It is of significant importance for pathologists to search for images sharing similar content with the query WSI, especially in the case-based diagnosis. While slide-level retrieval could be more intuitive and practical in clinical applications, most methods are designed for patch-level retrieval. A few recently unsupervised slide-level methods only focus on integrating patch features directly, without perceiving slide-level information, and thus severely limits the performance of WSI retrieval. To tackle the issue, we propose a High-Order Correlation-Guided Self-Supervised Hashing-Encoding Retrieval (HSHR) method. Specifically, we train an attention-based hash encoder with slide-level representation in a self-supervised manner, enabling it to generate more representative slide-level hash codes of cluster centers and assign weights for each. These optimized and weighted codes are leveraged to establish a similarity-based hypergraph, in which a hypergraph-guided retrieval module is adopted to explore high-order correlations in the multi-pairwise manifold to conduct WSI retrieval. Extensive experiments on multiple TCGA datasets with over 24,000 WSIs spanning 30 cancer subtypes demonstrate that HSHR achieves state-of-the-art performance compared with other unsupervised histology WSI retrieval methods.

Deep Brain Stimulation for Chronic Facial Pain: An Individual Participant Data (IPD) Meta-Analysis.

Despite available, advanced pharmacological and behavioral therapies, refractory chronic facial pain of different origins still poses a therapeutic challenge. In circumstances where there is insufficient responsiveness to pharmacological/behavioral therapies, deep brain stimulation should be considered as a potential effective treatment option. We performed an individual participant data (IPD) meta-analysis including searches on PubMed, Embase, and the Cochrane Library (2000-2022). The primary endpoint was the change in pain intensity (visual analogue scale; VAS) at a defined time-point of ≤3 months post-DBS. In addition, correlation and regression analyses were performed to identify predictive markers (age, duration of pain, frequency, amplitude, intensity, contact configuration, and the DBS target). A total of seven trials consisting of 54 screened patients met the inclusion criteria. DBS significantly reduced the pain levels after 3 months without being related to a specific DBS target, age, contact configuration, stimulation intensity, frequency, amplitude, or chronic pain duration. Adverse events were an infection or lead fracture (19%), stimulation-induced side effects (7%), and three deaths (unrelated to DBS-from cancer progression or a second stroke). Although comparable long-term data are lacking, the current published data indicate that DBS (thalamic and PVG/PAG) effectively suppresses facial pain in the short-term. However, the low-quality evidence, reporting bias, and placebo effects must be considered in future randomized-controlled DBS trials for facial pain.

Enzymatically-mineralized double-network hydrogels with ultrahigh mechanical strength, toughness, and stiffness.

Background: Synthetic hydrogels are commonly mechanically weak which limits the scope of their applications. Methods: In this study, we synthesized an organic-inorganic hybrid hydrogel with ultrahigh strength, stiffness, and toughness via enzyme-induced mineralization of calcium phosphate in a double network of bacterial cellulose nanofibers and alginate-Ca2+. Results: Cellulose nanofibers formed the first rigid network via hydrogen binding and templated the deposition of calcium phosphate, while alginate-Ca2+ formed the second energy-dissipating network via ionic interaction. The two networks created a brick-mortar-like structure, in which the "tortuous fracture path" mechanism by breaking the interlaced calcium phosphate-coated bacterial cellulose nanofibers and the hysteresis by unzipping the ionic alginate-Ca2+ network made a great contribution to the mechanical properties of the hydrogels. Conclusion: The optimized hydrogel exhibited ultrahigh fracture stress of 48 MPa, Young's modulus of 1329 MPa, and fracture energy of 3013 J/m2, which are barely possessed by the reported synthetic hydrogels. Finally, the hydrogel represented potential use in subchondral bone defect repair in an ex vivo model.

Genetic and Phenotypic Characterization of Multidrug-Resistant Klebsiella pneumoniae from Liver Abscess.

Cooccurrence of multidrug resistant (MDR) and hypervirulence phenotypes in liver abscess-causing Klebsiella pneumoniae (LAKp) would pose a major threat to public health. However, relatively little information is available on the genomic and phenotypic characteristics of this pathogen. This study aimed to investigate the virulence and resistance phenotype and genotype of MDR LAKp strains from 2016 to 2020. We collected 18 MDR LAKp strains from 395 liver abscess samples and characterized these strains using antimicrobial susceptibility test, string test, mucoviscosity assay, biofilm formation assay, Galleria mellonella killing assay, and whole-genome sequencing. Besides, phylogenetic and comparative genomic analyses were performed on these MDR LAKp, along with 94 LAKp genomes from global sources. Most of these MDR LAKp strains exhibited resistance to cephalosporins, quinolones, and chloramphenicol. Virulence assays revealed that only half of MDR LAKp strains exhibited higher virulence than classical MDR strain K. pneumoniae MGH78578. Importantly, we identified three ST11 KL64 hypervirulence carbapenem-resistant strains carrying blaKPC-2 and one colistin-resistant strain carrying mcr-1. Phylogenetic analysis revealed that 112 LAKp genomes were divided into two clades, and most of MDR LAKp strains in this study belonged to clade 1 (83.33%, 15/18). We also detected the loss of mucoviscosity mediated by mutations and ISKpn14 insertion in rmpA, and the latter representing a novel mechanism by which bacteria regulate RmpA system. This study provides novel insights into MDR LAKp and highlights the necessity for measures to prevent further spread of such organisms in hospital settings and the community. IMPORTANCE Pyogenic liver abscess is a potentially life-threatening suppurative infection of hepatic parenchyma. K. pneumoniae has emerged as a predominant pathogen of pyogenic liver abscess. Liver abscess-causing K. pneumoniae is generally considered hypervirulent K. pneumoniae and is susceptible to most antibiotics. Recently, convergence of multidrug resistant and hypervirulence phenotypes in liver abscess-causing K. pneumoniae was emerging and poses a major threat to public health. However, relatively little information is available on liver abscess-causing multidrug-resistant hypervirulent K. pneumoniae. In this study, we characterized phenotype and genotype of virulence and resistance of 18 multidrug-resistant hypervirulent liver abscess-causing K. pneumoniae strains collected from 395 pyogenic liver abscess cases in a tertiary teaching hospital over a 5-year period to enable in-depth understanding of this pathogen.