Metal chalcogenophosphates are receiving increasing interest, specifically as promising infrared nonlinear optical (NLO) candidates. Here, a rare‐earth chalcogenophosphate Eu2P2S6 crystallizing in ...the monoclinic noncentrosymmetric space group Pn was synthesized using a high‐temperature solid‐state method. Its structure features isolated P2S64− dimer, and two types of EuS8 bicapped triangular prisms. Eu2P2S6 exhibits a phase‐matchable second‐harmonic generation (SHG) response ≈0.9×AgGaS2@2.1 μm, and high laser‐induced damage threshold of 3.4×AgGaS2, representing the first rare‐earth NLO chalcogenophosphate. The theoretical calculation result suggests that the SHG response is ascribed to the synergetic contribution of P2S64− dimers and EuS8 bicapped triangular prisms. This work provides not only a promising high‐performance infrared NLO material, but also opens the avenue for exploring rare‐earth chalcogenophosphates as potential IR NLO materials.
Eu2P2S6 exhibits excellent NLO properties, including a phase‐matchable second‐harmonic generation (SHG) response ≈0.9×AgGaS2@2.1 μm, and a high laser‐induced damage threshold of 3.4×AgGaS2. Eu2P2S6 is the first NLO‐active rare‐earth‐based chalcogenophosphate.
Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully ...understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3–13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4
+
and/or CD8
+
T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4
+
and CD8
+
T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.
Trial registration
ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).
The transition form factors for doubly heavy baryons into a spin-1/2 or spin-3/2 ground-state baryon induced by both the charged current and the flavor changing neutral current are systematically ...studied within the light-front quark model. In the transition the two spectator quarks have two spin configurations and both are considered in this calculation. We use an updated vertex functions, and inspired by the flavor SU(3) symmetry, we also provide a new approach to derive the flavor-spin factors. With the obtained transition form factors, we perform a phenomenological study of the corresponding semi-leptonic decays of doubly heavy baryons induced by the
c
→
d
/
s
ℓ
+
ν
,
b
→
c
/
u
ℓ
-
ν
¯
and
b
→
d
/
s
ℓ
+
ℓ
-
. Results for partial decay widths, branching ratios and the polarization ratios
Γ
L
/
Γ
T
s are given. We find that most branching ratios for the semi-leptonic decays induced by the
c
→
d
,
s
transitions are at the order of
10
-
3
∼
10
-
2
, which might be useful for the search of other doubly-heavy baryons. Uncertainties in form factors, the flavor SU(3) symmetry and sources of symmetry breaking effects are discussed. We find that the SU(3) symmetry breaking effects could be sizable in charmed baryon decays while in the bottomed case, the SU(3) symmetry breaking effects are less significant. Our results can be examined at the experimental facilities in the future.
Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in ...our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
ObjectiveType 2 diabetes mellitus is increasing in young adults, and greater adiposity is considered a major risk factor. However, whether there is an association between obesity and diabetes and how ...this might be impacted by age is not clear. Therefore, we investigated the association between body mass index (BMI) and diabetes across a wide range of age groups (20–30, 30–40, 40–50, 50–60, 60–70 and ≥70 years old).DesignWe performed a retrospective cohort study using healthy screening programme data.SettingA total of 211 833 adult Chinese persons >20 years old across 32 sites and 11 cities in China (Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, Nantong) were selected for the study; these persons were free of diabetes at baseline.Primary and secondary outcome measuresFasting plasma glucose levels were measured and information regarding the history of diabetes was collected at each visit. Diabetes was diagnosed as fasting plasma glucose ≥7.00 mmol/L and/or self-reported diabetes. Patients were censored at the date of diagnosis or the final visit, whichever came first.ResultsWith a median follow-up of 3.1 years, 4174 of the 211 833 participants developed diabetes, with an age-adjusted incidence rate of 7.35 per 1000 persons. The risk of incident diabetes increased proportionally with increasing baseline BMI values, with a 23% increased risk of incident diabetes with each kg/m2 increase in BMI (95% CI 1.22 to 1.24). Across all age groups, there was a linear association between BMI and the risk of incident diabetes, although there was a stronger association between BMI and incident diabetes in the younger age groups (age×BMI interaction, p<0.0001).ConclusionsAn increased BMI is also independently associated with a higher risk of developing diabetes in young adults and the effects of BMI on incident diabetes were accentuated in younger adults.
As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the ...reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high‐performance MXene image sensor array fabricated by a wafer‐scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin‐coating, photolithography, and dry‐etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large‐area patterning methods reported previously. As a result, a high‐density integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light–dark current ratio (Ilight/Idark) of 6.22 × 106, which is the ultrahigh value among all reported MXene‐based photodetectors, is fabricated. This patterning technique paves a way for large‐scale high‐performance MXetronics compatible with mainstream semiconductor processes.
MXenes are promising for future electronics and optoelectronics; however, previously reported patterning methods lack efficiency, resolution, and compatibility with mainstream semiconductor processing. Here, a wafer‐scale combination patterning method with a resolution up to the micrometer scale is developed, resulting in an integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a record‐high detectivity of 7.73 × 1014 Jones.
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•Recent progresses made in the development of phthalocyanines for photodynamic therapy are outlined.•Representative water-soluble phthalocyanines are presented.•Main targeting ...strategies are discussed.•Future challenges are also presented.
Owing to their high extinction coefficients, long absorption wavelengths, and modification tunable photophysical and photochemical properties, phthalocyanines (Pcs) have been widely used as photosensitizers for photodynamic therapy (PDT). Advances made in the past five years on the development of Pcs as medicinal photosensitizers are reviewed and the main design considerations for medicinal applications of these substances are discussed.
Acute kidney injury (AKI) is a common and severe clinical condition with high morbidity and mortality. Ischaemia‐reperfusion (I/R) injury remains the major cause of AKI in the clinic. Ferroptosis is ...a recently discovered form of programmed cell death (PCD) that is characterized by iron‐dependent accumulation of reactive oxygen species (ROS). Compelling evidence has shown that renal tubular cell death involves ferroptosis, although the underlying mechanisms remain unclear. Augmenter of liver regeneration (ALR) is a widely distributed multifunctional protein that is expressed in many tissues. Our previous study demonstrated that ALR possesses an anti‐oxidant function. However, the modulatory mechanism of ALR remains unclear and warrants further investigation. Here, to elucidate the role of ALR in ferroptosis, ALR expression was inhibited using short hairpin RNA lentivirals (shRNA) in vitro model of I/R‐induced AKI. The results suggest that the level of ferroptosis is increased, particularly in the shRNA/ALR group, accompanied by increased ROS and mitochondrial damage. Furthermore, inhibition of system xc‐ with erastin aggravates ferroptosis, particularly silencing of the expression of ALR. Unexpectedly, we demonstrate a novel signalling pathway of ferroptosis. In summary, we show for the first time that silencing ALR aggravates ferroptosis in an in vitro model of I/R. Notably, we show that I/R induced kidney ferroptosis is mediated by ALR, which is linked to the glutathione‐glutathione peroxidase (GSH‐GPx) system.
Tin diselenide (SnSe2) nanosheets as novel 2D layered materials have excellent optical properties with many promising application prospects, such as photoelectric detectors, nonlinear optics, ...infrared photoelectric devices, and ultrafast photonics. Among them, ultrafast photonics has attracted much attention due to its enormous advantages; for instance, extremely fast pulse, strong peak power, and narrow bandwidth. In this work, SnSe2 nanosheets are fabricated by using solvothermal treatment, and the characteristics of SnSe2 are systemically investigated. In addition, the solution of SnSe2 nanosheets is successfully prepared as a fiber‐based saturable absorber by utilizing the evanescent field effect, which can bear a high pump power. 31st‐order subpicosecond harmonic mode locking is generated in an Er‐doped fiber laser, corresponding to the maximum repetition rate of 257.3 MHz and pulse duration of 887 fs. The results show that SnSe2 can be used as an excellent nonlinear photonic device in many fields, such as frequency comb, lasers, photodetectors, etc.
Tin diselenide (SnSe2) nanosheets as novel 2D layered materials have excellent optical properties. SnSe2 nanosheets fabricated by using solvothermal treatment are successfully prepared as fiber‐based saturable absorbers by utilizing the evanescent field effect, which can bear a high pump power. 31st‐order subpicosecond harmonic mode‐locking is generated, corresponding to 257.3 MHz repetition rate.
Astrocytes are crucial regulators in the central nervous system. Abnormal activation of astrocytes contributes to some behavior deficits. However, mechanisms underlying the effects remain unclear. ...Here, we studied the activation of A1 astrocytes and their contribution to murine behavior deficits.
A1 astrocytes were induced by treatment with lipopolysaccharide (LPS) in vitro. The functional phenotype of astrocytes was determined by quantitative RT-PCR, ELISA, and immunohistochemistry. To assess the role of A1 astrocytes in vivo, mice were injected intraperitoneally with LPS. Then, murine behaviors were tested, and the hippocampus and cortex were analyzed by quantitative RT-PCR, ELISA, and immunohistochemistry. The function of IL-10 and fluorocitrate on A1 astrocyte activation was also examined.
Our results show that astrocytes isolated from B6.129S6-Il10
/J homozygotes (IL-10
) were prone to characteristics of A1 reactive astrocytes. Compared with their wild-type counterparts, IL-10
astrocytes exhibited higher expression of glial fibrillary acidic protein (GFAP). Whether or not they were stimulated with LPS, IL-10
astrocytes exhibited enhanced expression of A1-specific transcripts and proinflammatory factors IL-1β, IL-6, and TNFα. In addition, IL-10
astrocytes demonstrated hyperphosphorylation of STAT3. Moreover, astrocytes from IL-10
mice showed attenuated phagocytic ability and were neurotoxic. IL-10
mice demonstrated increased immobility time in the forced swim test and defective learning and memory behavior in the Morris water maze test. Moreover, enhanced neuroinflammation was found in the hippocampus and cortex of IL-10
mice, accompanying with more GFAP-positive astrocytes and severe neuron loss in the hippocampus. Pretreatment IL-10
mice with IL-10 or fluorocitrate decreased the expression of proinflammatory factors and A1-specific transcripts in the hippocampus and cortex, and then alleviated LPS-induced depressive-like behavior.
These results demonstrate that astrocytes isolated from B6.129S6-Il10
/J homozygotes are prone to A1 phenotype and contribute to the depression-like behavior and memory deficits. Inhibiting A1 astrocyte activation may be an attractive therapeutic strategy in some neurodegenerative diseases.
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