Viable Vitreous Grafts of Whole Porcine Menisci for Transplant in the Knee and Temporomandibular Joints.

The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (>3 mL) due to challenges in CPA penetration. Dense avascular meniscus tissues require extended CPA exposure for adequate penetration; however, prolonged exposure becomes cytotoxic. Balancing penetration and reducing cell toxicity is required. To overcome this hurdle, a simulation-based optimization approach is developed by combining computational modeling with microcomputed tomography (µCT) imaging to predict 3D CPA distributions within tissues over time accurately. This approach minimizes CPA exposure time, resulting in 85% viability in 4-mL meniscal specimens, 70% in 10-mL whole knee menisci, and 85% in 15-mL whole TMJ menisci (i.e., TMJ disc) post-vitrification, outperforming slow-freezing methods (20%-40%), in a pig model. The extracellular matrix (ECM) structure and biomechanical strength of vitreous tissues remain largely intact. Vitreous meniscus grafts demonstrate clinical-level viability (≥70%), closely resembling the material properties of native tissues, with long-term availability for transplantation. The enhanced vitrification technology opens new possibilities for other avascular grafts.

The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS: This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS: Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS: Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

iPSC-Derived Airway Epithelial Cells: Progress, Promise, and Challenges.

Induced pluripotent stem cells (iPSCs) generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide an unlimited source of cells that can be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. This review gives a comprehensive overview of recent progress toward the use of iPSCs to generate proximal and distal airway epithelial cells and mix lung organoids. Furthermore, their potential applications and future challenges for the field are discussed, with a focus on the technological hurdles that must be cleared before stem cell therapeutics can be used for clinical treatment.

Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Highly Sensitive Capacitive Flexible Pressure Sensor Based on a High-Permittivity MXene Nanocomposite and 3D Network Electrode for Wearable Electronics.

With the fast development of consumer electronic and artificial intelligence equipment, flexible pressure sensors (FPSs) have become a momentous component in the application of wearable electronic, electronic skin, and human-machine interfacing. The capacitive FPS possesses the merits of low energy consumption, high resolution, and fast dynamic response, so it is ideal for mobile and wearable electronics. However, capacitive FPS is vulnerable to electromagnetic interference and parasitic capacitance due to its low sensitivity. Microstructure or porous dielectric materials have been applied to improve the sensitivity of the capacitive FPS, but the high sensitivity is just limited to a narrow region. In this work, we propose a different strategy that incorporates a high-permittivity MXene nanocomposite dielectric with a 3D network electrode (3DNE) to improve the sensing performance of the capacitive FPS. Thanks to the high permittivity of the dielectric layer and hierarchical deformation of the electrode, the fabricated capacitive FPS exhibits a high sensitivity of 10.2 kPa-1 in the low pressure range (0-8.6 kPa) and still maintains a relatively high sensitivity of 3.65 kPa-1 with a near-linear response in a wide pressure range (8.6-100 kPa). In addition, the capacitive FPS can withstand over 20,000 times pressure loads without significant signal damping. Furthermore, the working mechanism of the capacitive FPS is illustrated by the finite element analysis (FEA) method and theoretical calculation. The application potential of the sensor in wearable electronics was demonstrated by human pulse wave monitoring and pressure mapping tests with a 4 × 6 sensor microarray.

Rational design and synthesis of 6-aryl-6H-benzo[c]chromenes as non-steroidal progesterone receptor antagonists for use against cancers.

Progesterone receptor (PR) antagonists have been found to be effective for treating certain human cancers. However, the steroidal structure of PR antagonists could bind to other hormone receptors, thus leading to serious side effects. On the other hand, non-steroidal PR antagonists have rarely been evaluated for their anti-cancer efficacy. Therefore, identifying novel non-steroidal PR antagonists possessing potent anti-cancer efficacy would be an attractive project to pursue. In this study, we presented a new metal-free oxidative CH arylation method to rapidly synthesize a series of 6-aryl-6H-benzo[c]chromene derivatives. Multiple cancer cell lines were used for their anti-cancer activity screening. An extensive analysis of structure-activity relationships (SAR) of the derivatives revealed that compounds 32 and 34 markedly inhibited the proliferation of MCF-7 cells with IC50 values of 6.32 ± 0.52 µM and 5.71 ± 0.49 µM, respectively. Further investigation indicated that derivatives 32 and 34 could elevate the expression of p21 and decrease the expressions of CDK4 and cyclin D1, leading to cell cycle arrest at G0/G1 phase. In addition, derivatives 32 and 34 could induce apoptosis of MCF-7 cells in both dose- and time-dependent manners by activation of p53 pathway, i.e., activation of Cleaved Caspase-3, p53 and P-p53 as well as elevation of the Bax/Bcl-2 ratio. Docking of derivatives 32 and 34 into a PR homology model exhibited potent PR antagonistic activity indicating the 6-aryl-6H-benzo[c]chromene derivatives are promising PR antagonists. We envisioned that derivatives 32 and 34 might be potential anti-cancer drug candidates as novel therapeutic treatment for breast cancer.

Downregulation of lncRNA-11496 in the Brain Contributes to Microglia Apoptosis via Regulation of Mef2c in Chronic T. gondii Infection Mice.

Though it is well known that chronic infections of Toxoplasma gondii (T. gondii) can induce mental and behavioral disorders in the host, little is known about the role of long non-coding RNAs (lncRNAs) in this pathological process. In this study, we employed an advanced lncRNAs and mRNAs integration chip (Affymetrix HTA 2.0) to detect the expression of both lncRNAs and mRNAs in T. gondii Chinese 1 strain infected mouse brain. As a result, for the first time, the downregulation of lncRNA-11496 (NONMMUGO11496) was identified as the responsible factor for this pathological process. We showed that dysregulation of lncRNA-11496 affected proliferation, differentiation and apoptosis of mouse microglia. Furthermore, we proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. In a more detailed study, we confirmed that lncRNA-11496 positively regulated the expression of Mef2c by binding to histone deacetylase 2 (HDAC2). Importantly, Mef2c itself could coordinate neuronal differentiation, survival, as well as synapse formation. Thus, our current study provides the first evidence in terms of the modulatory action of lncRNAs in chronic toxoplasmosis in T. gondii infected mouse brain, providing a solid scientific basis for using lncRNA-11496 as a therapeutic target to treat T. gondii induced neurological disorder.

Cellular localization of melatonin receptor Mel1b in pigeon retina.

Melatonin, an important neuromodulator involved in circadian rhythms, modulates a series of physiological processes via activating its specific receptors, namely Mel1a (MT1), Mel1b (MT2) and Mel1c receptors. In this work, the localization of Mel1b receptor was studied in pigeon retina using double immunohistochemistry staining and confocal scanning microscopy. Our results showed that Mel1b receptor widely existed in the outer segment of photoreceptors and in the somata of dopaminergic amacrine cells, cholinergic amacrine cells, glycinergic AII amacrine cells, conventional ganglion cells and intrinsically photosensitive retinal ganglion cells, while horizontal cells, bipolar cells and Müller glial cells seemed to lack immunoreactivity of Mel1b receptor. That multiple types of retinal cells expressing Mel1b receptor suggests melatonin may directly modulate the activities of retina via activating Mel1b receptor.

High-Performance Self-Powered Ultraviolet Photodetector Based on Nano-Porous GaN and CoPc p-n Vertical Heterojunction.

Gallium nitride (GaN) is a superior candidate material for fabricating ultraviolet (UV) photodetectors (PDs) by taking advantage of its attractive wide bandgap (3.4 eV) and stable chemical and physical properties. However, the performance of available GaN-based UV PDs (e.g., in terms of detectivity and sensitivity) still require improvement. Fabricating nanoporous GaN (porous-GaN) structures and constructing organic/inorganic hybrids are two effective ways to improve the performance of PDs. In this study, a novel self-powered UV PD was developed by using p-type cobalt phthalocyanine (CoPc) and n-type porous-GaN (CoPc/porous-GaN) to construct a p-n vertical heterojunction via a thermal vapor deposition method. Under 365 nm 0.009 mWcm-2 light illumination, our device showed a photoresponsivity of 588 mA/W, a detectivity of 4.8 × 1012 Jones, and a linear dynamic range of 79.5 dB, which are better than CoPc- and flat-GaN (CoPc/flat-GaN)-based PDs. The high performance was mainly attributed to the built-in electric field (BEF) generated at the interface of the CoPc film and the nanoporous-GaN, as well as the nanoporous structure of GaN, which allows for a higher absorptivity of light. Furthermore, the device showed excellent stability, as its photoelectrical property and on/off switching behavior remained the same, even after 3 months.

A nanocomposite consisting of ZnO decorated graphene oxide nanoribbons for resistive sensing of NO2 gas at room temperature.

A composite prepared from zinc oxide and graphene oxide nanoribbons (ZnO/GONR) is demonstrated to enable improved room temperature (RT) detection of nitrogen dioxide (NO2). Low-cost hydrothermal synthesis is used to construct the composite. The properties of the resistive sensor, including the sensitivity, response and recovery times, repeatability and selectivity, were investigated in the NO2 concentration range from 1 to 50 ppm at RT. The sensor, typically operated at a voltage of 5 V, exhibits a low detection limit of 1 ppm, a fast response-recovery time, and excellent repeatability which outperforms that of pure ZnO sensors. The sensing mechanism is explained in terms of a redox reaction between NO2 and oxygen anions on the surface of the ZnO/GONR composite. Graphical abstract Schematic representation of the NO2 sensing mechanisms on the surface of the ZnO/GONR composite and overall improved NO2 gas-sensing performance.

Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice.

There is no effective protective vaccine against human toxoplasmosis, which is a potential threat to nearly a third of the world population. Vaccines based on virus-like particles (VLPs) have been highly successful in humans for many years, but have rarely been applied against Toxoplasma gondii infection. In this study, we inserted a B cell epitope (SAG182-102 or SAG1301-320), a CD8+ cell epitope (HF10 or ROP7), and a CD4+ cell epitope (AS15) of T. gondii into a truncated HBcΔ(amino acids1-149) particle to construct four chimeric VLP vaccine formulations, i.e., HBcΔH82, HBcΔH301, HBcΔ R82, and HBcΔ R301. When these chimeric HBc particles were expressed in Escherichia coli, they showed icosahedral morphology similar to that of the original VLPs and were evaluated as vaccine formulations against acute and chronic toxoplasmosis in a mouse model (BALB/c mice (H-2d). All these chimeric HBc VLPs induced strong humoral and cellular immune responses with high IgG antibody titers and interferon(IFN)-γ production. Only the mice immunized with HBcΔH82 showed prolonged survival time (15.6 ± 3.8 vs. 5.6 ± 0.8 days) against acute infection with RH tachyzoites and decrease in brain parasite load (1,454 ± 239 vs. 2,091 ± 263) against chronic infection with Prugniuad cysts, as compared to the findings for the control group. These findings suggest that HBc VLPs would act as an effective carrier for delivering effective multiple antigenic epitopes and would be beneficial for developing a safe and long-acting vaccine against toxoplasmosis.

Electrodeposition of Pd-Pt Nanocomposites on Porous GaN for Electrochemical Nitrite Sensing.

In recent years, nitrite pollution has become a subject of great concern for human lives, involving a number of fields, such as environment, food industry and biological process. However, the effective detection of nitrite is an instant demand as well as an unprecedented challenge. Here, a novel nitrite sensor was fabricated by electrochemical deposition of palladium and platinum (Pd-Pt) nanocomposites on porous gallium nitride (PGaN). The obtained Pd-Pt/PGaN sensor provides abundant electrocatalytic sites, endowing it with excellent performances for nitrite detection. The sensor also shows a low detection limit of 0.95 µM, superior linear ampere response and high sensitivity (150 µA/mM for 1 to 300 µM and 73 µA/mM for 300 to 3000 µM) for nitrite. In addition, the Pd-Pt/PGaN sensor was applied and evaluated in the determination of nitrite from the real environmental samples. The experimental results demonstrate that the sensor has good reproducibility and long-term stability. It provides a practical way for rapidly and effectively monitoring nitrite content in the practical application.

A ZnO/porous GaN heterojunction and its application as a humidity sensor.

A heterojunction of ZnO/porous GaN (ZnO/PGAN) was fabricated and directly applied to a diode-type humidity sensor. ZnO disks were loaded onto PGAN using a spraying process. The structure and surface morphology of the ZnO/PGAN were characterized using X-ray diffraction and scanning electron microscopy. The heterojunction displayed an excellent diode nature, which was investigated using photoluminescence spectra and I-V characteristics. The excellent transport capability of ZnO/PGAN contributes to enhanced electron transfer, and hence results in high sensitivity and quick response/recovery properties under different relative humidity (RH) levels. In the range of 12-96% RH, a fast sensing response time as low as 7 s and a recovery time of 13 s can be achieved. The simple design of a ZnO/PGAN based humidity sensor highlights its potential in various applications.

Fabrication of a cobalt phthalocyanine free-standing film on an ionic liquid surface for memory device applications.

The fabrication of a metal phthalocyanine (MPc) film with good transferability and exploitation of its properties are very important for further application. In this study, a continuous free-standing film of CoPc was obtained on an ionic liquid (IL) surface via a physical vapor deposition (PVD) method. The as-obtained film has a ß-phase structure and is constructed with one dimensional CoPc to form a network structure. The morphology of the film could be easily tuned by tunning the flow rate of the carrier gas. More importantly, the device based on these films shows obvious electrical switching and negative differential resistance (NDR) characteristics. The maximum ON/OFF current ratio of two distinctive conductivity states is ∼100 at a reading voltage of +30 V. The conductivity and conductive switching behavior of the NW constructed device are better than the device constructed with NRs. The NDR effect and electrical switching conduction mechanism can be explained by the charge trap elements of the CoII/CoI redox couples. The above results open up the possibility of CoPc as a memory medium for information storage and logic circuits applications.

Wearable Wide-Range Strain Sensors Based on Ionic Liquids and Monitoring of Human Activities.

Wearable sensors for detection of human activities have encouraged the development of highly elastic sensors. In particular, to capture subtle and large-scale body motion, stretchable and wide-range strain sensors are highly desired, but still a challenge. Herein, a highly stretchable and transparent stain sensor based on ionic liquids and elastic polymer has been developed. The as-obtained sensor exhibits impressive stretchability with wide-range strain (from 0.1% to 400%), good bending properties and high sensitivity, whose gauge factor can reach 7.9. Importantly, the sensors show excellent biological compatibility and succeed in monitoring the diverse human activities ranging from the complex large-scale multidimensional motions to subtle signals, including wrist, finger and elbow joint bending, finger touch, breath, speech, swallow behavior and pulse wave.

Direct physical vapor deposition and flexible photoelectrical properties of large-area free-standing films of metal octaethylporphyrin on ionic liquid surface.

Free-standing films of metal octaethylporphyrins (MOEPs) were prepared for the first time by a physical vapor deposition on surface of an ionic liquid (IL). Different from those on solid surfaces, the as-obtained films were very compact and with plannar structure. The monitoring of time-dependent process indicated that the high surface energy of IL and the strong π…π interaction between MOEP molecules played key roles in forming such films. Furthermore, the as-obtained film showed good transferability, which made it possible to be easily transferred to any substrates for further device application. More importantly, the prototype photodetectors based on free-standing films of MOEP showed ultra flexibility, mechanical stability, and durability.

Electrosynthesis of bismuth nanodendrites/gallium nitride electrode for non-enzymatic hydrogen peroxide detection.

Bismuth nanodendrites (BiNDs) were electrodeposited on planar gallium nitride (GaN) electrode via a differential pulse voltammetric technique to fabricate the non-enzymatic hydrogen peroxide (H2O2) sensor. SEM images revealed that the as-obtained BiNDs had numerous dendrite sub-branches, whose diameters ranged from 136 to 152nm. The BiNDs/GaN electrode showed linear amperometric responses for H2O2 in the concentration range from 10µM to 1mM with the sensitivity of 60.0µAmM-1cm-2. Another linear range was from 1 to 10mM with the sensitivity of 23.3µAmM-1cm-2. The limit of detection (LOD) was 5µM with the signal-to-noise ratio of 3. The applicability of the sensor was investigated to the H2O2 detection in real samples such as fetal bovine serum and milk, and the sensor exhibited excellent anti-interference capacity. The achieved results indicate that the as-prepared BiNDs/GaN sensor with good reproducibility and long-term stability was promising for detecting H2O2 in practical environments.

Fever of unknown origin revealed to be primary splenic lymphoma: A rare case report with review of the literature.

Fever is a common clinical presentation of a number of diseases. A sustained unexplained fever >38.3°C lasting for >3 weeks without an established diagnosis despite intensive diagnostic evaluation is referred to as fever of unknown origin (FUO). FUO remains a clinical challenge for physicians, as it may be attributed to a wide range of disorders, mainly infections, malignancies, non-infectious inflammatory diseases and miscellaneous diseases. We herein report the case of a 59-year-old male patient who presented with prolonged unexplained fever and was found to have a diffusely enlarged hypermetabolic spleen, as shown on 18F-fluorodeoxyglucose positron emission tomography/computed tomography examination. Following splenectomy, histopathological examination revealed primary splenic lymphoma (PSL) of B-cell origin. The patient received 6 courses of systemic chemotherapy with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine and prednisone (R-ECHOP regimen) and responded well to treatment. Thus, in patients with FUO and splenomegaly, the possibility of PSL should be taken into consideration.

Porous GaN electrode for anodic stripping voltammetry of silver(I).

Here we demonstrate porous GaN electrode can be applied for trace Ag(I) detection. Compared to traditional planar electrodes, porous GaN electrode can detect lower concentration of Ag(I) as it possesses more deposition sites (crystal defects) and larger surface area. Under the optimum conditions, porous GaN electrode shows a linear voltammetric response in the Ag(I) concentration range from 1 to 100ppb with the detection limit of 0.5ppb. Such an unmodified, high-porosity and chemically stable electrode is promising to operate in real samples.

Correction: Large-size nanosheets of 9,10-bis(phenylethynyl)anthracene with high photoresponse and light emission anisotropy.

Correction for 'Large-size nanosheets of 9,10-bis(phenylethynyl)anthracene with high photoresponse and light emission anisotropy' by Juan-Ye Wang et al., Phys. Chem. Chem. Phys., 2016, DOI: 10.1039/c5cp05507e.