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Bi2 Te3 -based solid solutions, which have been widely used as thermoelectric (TE) materials for the room temperature TE refrigeration, are also the potential candidates for the power generators with medium and low-temperature heat sources. Therefore, depending on the applications, Bi2 Te3 -based materials are expected to exhibit excellent TE properties in different temperature ranges. Manipulating the point defects in Bi2 Te3 -based materials is an effective and important method to realize this purpose. In this review, we focus on how to optimize the TE properties of Bi2 Te3 -based TE materials in different temperature ranges by defect engineering. Our calculation results of two-band model revel that tuning the carrier concentration and band gap, which is easily realized by defects engineering, can obtain better TE properties at different temperatures. Then, the typical paradigms about optimizing the TE properties at different temperatures for n-type and p-type Bi2 Te3 -based ZM ingots and polycrystals are discussed in the perspective of defects engineering. This review can provide the guidance to improve the TE properties of Bi2 Te3 -based materials at different temperatures by defects engineering.

Bi2Se3, a sister compound of the best room-temperature thermoelectric (TE) Bi2Te3, has been proven to undergo a transition from a rhombohedral phase to an orthorhombic phase by Sb-alloying. Te-free...

p-Type FeNbSb-based half-Heusler compounds exhibit promising thermoelectric (TE) performance under high temperatures. Herein, the optimal sintering temperature and pressure of these compounds were determined. Sintering temperature can affect relative density, and consequently, improve TE performance. In addition, a series of Sn-doped FeNbSb compounds was prepared in accordance with the optimal sintering temperature and pressure. Results showed that Sn optimized the power factor and reduced lattice thermal conductivity by enhancing point defect phonon scattering. A high ZT of 0.66 was attained at 923 K for FeNbSb0.84Sn0.16. The findings of this study lay the foundation for reducing the thermal conductivity of FeNbSb-based compounds.

Sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. As our closest phylogenetic relatives, non-human primates (NHPs) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. Previous work on measuring sleep in NHPs has mostly used electroencephalography or videography. In this study, simultaneous videography and actigraphy were applied to observe sleep patterns in 10 cynomolgus monkeys ( Macaca fascicularis) over seven nights (12 h per night). The durations of wake, transitional sleep, and relaxed sleep were scored by analysis of animal behaviors from videography and actigraphy data, using the same behavioral criteria for each state, with findings then compared. Here, results indicated that actigraphy constituted a reliable approach for scoring the state of sleep in monkeys and showed a significant correlation with that scored by videography. Epoch-by-epoch analysis further indicated that actigraphy was more suitable for scoring the state of relaxed sleep, correctly identifying 97.57% of relaxed sleep in comparison with video analysis. Only 34 epochs (0.13%) and 611 epochs (2.30%) were differently interpreted as wake and transitional sleep compared with videography analysis. The present study validated the behavioral criteria and actigraphy methodology for scoring sleep, which can be considered as a useful and a complementary technique to electroencephalography and/or videography analysis for sleep studies in NHPs.

(Bi,Sb)2(Te,Se)3 alloys are widely used commercial thermoelectric (TE) materials for solid-state refrigeration around room temperature. The composition-induced structural phase transition could be realized by varying the compositions in these alloys, which may largely alter the electronic structure and phonon dispersion. Among them, the Se-alloyed Sb2Te3 accompanied with structural transition is seldom reported. Herein, the interrelations of Se-alloying induced changes in structural phase transition, band structure and TE properties of p-type zone-melted Sb2Te3-xSex (x = 1.5–2.4) alloys near phase transition boundary are systematically investigated. The results demonstrate that Sb2Te3-xSex shows a structural transition from a rhombohedral phase to mixed structure at x = 2.0. The carrier concentration and bandgap at room temperature of Sb2Te3-xSex (x = 1.5–2.4) constantly decrease with increasing Se contents x. The zT peak of the Sb2TeSe2 matrix is improved and shifted to higher temperature by optimizing carrier concentration via Ag doping. A maximum zT of ∼0.4 is obtained at 680 K in Sb1.97Ag0.03TeSe2 alloy, about 100% enhancement compared with the undoped sample. Keywords: Thermoelectric materials, Zone melting, Structural transition, Doping, Thermoelectric properties

During the manufacturing process of dielectric materials used in electromagnetic engineering, the electromagnetic parameters are often spatially uncertain due to the processing technology, environmental temperature, personal operations, etc. Traditionally, the random field model can be used to measure the spatial uncertainties, but its construction requires a large number of samples. On the contrary, the interval field model only needs the upper and lower bounds of the spatially uncertain parameters, which requires much less samples and furthermore is easy to understand and use for engineers. Therefore, in this paper, the interval field model is introduced to describe the spatial uncertainties of dielectric materials, and then an interval finite element method (IFEM) is proposed to calculate the upper and lower bounds of electromagnetic responses. Firstly, the interval field of the dielectric material is represented by the interval K-L expansion and inserted into the scalar Helmholtz wave equations, and thus the interval equilibrium equations are constructed according to the node-based finite element method. Secondly, a perturbation interval finite element method is developed for calculating the upper and lower bounds of electromagnetic responses such as the electric strength and magnetic strength. Finally, the effectiveness of the proposed method is verified by three numerical examples.

Multiple myeloma (MM) is still an incurable malignancy of plasma cells. Proteasome inhibitors (PIs) work as the backbone agent and have greatly improved the outcome in majority of newly diagnosed patients with myeloma. However, drug resistance remains the major obstacle causing treatment failure in clinical practice. Here, we investigated the effects of Indirubin-3'-monoxime (I3MO), one of the derivatives of Indirubin, in the treatment of MM.MM patient primary samples and human cell lines were examined. I3MO effects on myeloma treatment and the underling molecular mechanisms were investigated via in vivo and in vitro study.Our results demonstrated the anti-MM activity of I3MO in both drug- sensitive and -resistance MM cells. I3MO sensitizes MM cells to bortezomib-induced apoptosis. Mechanistically, I3MO acts as a multifaceted regulator of cell death, which induced DNA damage, cell cycle arrest, and abrogates NF-κB activation. I3MO efficiently down-regulated USP7 expression, promoted NEK2 degradation, and suppressed NF-κB signaling in MM. Our study reported that I3MO directly bound with and caused the down-regulation of PA28γ (PSME3), and PA200 (PSME4), the proteasome activators. Knockdown of PSME3 or PSME4 caused the inhibition of proteasome capacity and the overload of paraprotein, which sensitizes MM cells to bortezomib-mediated growth arrest. Clinical data demonstrated that PSME3 and PSME4 are over-expressed in relapsed/refractory MM (RRMM) and associated with inferior outcome.Altogether, our study indicates that I3MO is agent triggering proteasome inhibition and represents a promising therapeutic strategy to improve patient outcome in MM.A full list of funding can be found in the acknowledgements.

Endoplasmic reticulum stress-mediated apoptosis plays a vital role in the occurrence and development of heart failure. Dapagliflozin (DAPA), a new type of sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an oral hypoglycemic drug that reduces glucose reabsorption by the kidneys and increases glucose excretion in the urine. Studies have shown that DAPA may have the potential to treat heart failure in addition to controlling blood sugar. This study explored the effect of DAPA on endoplasmic reticulum stress-related apoptosis caused by heart failure. In vitro, we found that DAPA inhibited the expression of cleaved caspase 3, Bax, C/EBP homologous protein (CHOP), and glucose-regulated protein78 (GRP78) and upregulated the cardiomyoprotective protein Bcl-2 in angiotensin II (Ang II)-treated cardiomyocytes. In addition, DAPA promoted the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and suppressed the expression of activating transcription factor 4 (ATF4) and the ratios p-PERK/PERK and p-eIF2α/eIF2α. Notably, the therapeutic effect of DAPA was weakened by pretreatment with the SIRT1 inhibitor EX527 (10 μM). Simultaneous administration of DAPA inhibited the Ang II-induced transformation of fibroblasts into myofibroblasts and inhibited fibroblast migration. In summary, our present findings first indicate that DAPA could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in Ang II-treated cardiomyocytes and ameliorate heart failure development in vivo.

Objective: To assess the influence of PDCA-based nursing management model on the quality of life (QOL) and complications of patients with acute leukemia undergoing chemotherapy. Methods: In this study, we randomly divided 118 patients with acute leukemia undergoing chemotherapy in our hospital into an observation group (n=59) and a control group (n=59). The control group was implemented routine nursing while the observation group was implemented PDCA-based nursing management. The anxiety, depression, QOL, cancer fatigue, total complication rate, sleep quality, and patients’ satisfaction were compared between the two groups. Results: The SAS and SDS scores of the observation group were significantly lower than those of the control group (P

SnTe, as the nontoxic analogue to high-performance PbTe thermoelectric material, has captured the worldwide interest recently. Many triumphant instances focus on the strategies of band convergence, resonant doping, and nano-precipitates phonon scattering. Herein, the p-type SnTe-based materials Sn0.85−xSb0.15MgxTe (x = 0–0.10) are fabricated and a combined effect of Sb and Mg is investigated. Sb alloying tunes the hole carrier concentration of SnTe and decreases the lattice thermal conductivity. Mg alloying leads to a nearly hundredfold rise of disorder parameter due to the large mass and strain fluctuations, and as a consequence the lattice thermal conductivity decreases further down to ∼0.64 W m−1 K−1 at 773 K, close to the theoretical minimum of the lattice thermal conductivity (∼0.50 W m−1 K−1) of SnTe. In conjunction with the enhancement of the Seebeck coefficient caused by band convergence due to Mg alloying, the maximum zTmax reaches ∼1.02 and the device zTdevice of ∼0.50 at 773 K for Sn0.79Sb0.15Mg0.06Te, suggesting this SnTe-based composition has a promising potential in intermediate temperature thermoelectric applications.

Pristine GeTe shows promising thermoelectric performance but is limited by the high carrier concentration (nH) from Ge vacancies and thermal conductivity. Herein, Cu/Sb was chosen as codopants to suppress the high nH and to decrease thermal conductivity. In this condition, a promising zT of ∼1.62 under 773 K was acquired in the Ge0.85Te(CuSb)0.075 system proposed in this paper/work. Results show that as the dopant concentration increases, the power factor rises due to the reduction of the nH to ∼1 × 1020 cm–3. Apart from this, the total thermal conductivity also declines from ∼7.4 W m–1 K–1 to ∼1.59 W m–1 K–1 originating from an ultralow lattice thermal conductivity, in which the multiscatter mechanism from grain boundaries and point defect disperses the frequency phonons differently. The findings in this paper combine thermal and electronic strategies and lay the foundation to develop Pb-free thermoelectric materials.

The excellent p-type thermoelectric (TE) performance of ternary chalcopyrite I–III–IV2 originates from its distinctive crystal structure and superior electrical transport properties. Here, we applied the first-principles method and Boltzmann theory to calculate the electronic band structure and electrical transport performance of CuGaTe2. We also calculated the phonon spectrum and thermal conductivity of this material. The calculated lattice thermal conductivity of CuGaTe2 was higher than that of other TE materials given its large Debye temperature and low Gruneisen parameter. These characteristics proved that enhancing phonon scattering can effectively improve the TE performance of CuGaTe2. The predicted maximum zT value of p-type CuGaTe2 was 3.8 over the optimal carrier concentration range at 900 K and minimum lattice thermal conductivity. This value was considerably larger than previously reported experimental values. Given its high predicted zT, p-type CuGaTe2 is a promising TE material with potential applications in midtemperature power generation.

Vacancy defects on an iron surface have a great influence on the occurrence of hydrogen embrittlement. The adsorption/dissociation mechanism of H2S and the diffusion behavior of H atoms were calculated by first-principles spin-polarization density functional theory (DFT) on defect-free and vacancy-defective Fe(1 0 0) surfaces. The results show that the maximum dissociation energy barriers of H2S on the Fe(1 0 0) surface of defect-free and first-layer vacancy-defective Fe are 0.35 and 0.17 eV, respectively, indicating that the reactivity of the vacancy-defective Fe(1 0 0) surface is moderately increased. The existence of vacancy defects changes the preferential H atom diffusion entrance to the subsurface and shortens the diffusion path. For H diffusion in bulk Fe(1 0 0), it is found that H atoms diffuse via a tortuous path from one tetrahedral-site to a neighboring tetrahedral-site rather than diffusing through a linear trajectory. Moreover, the previously suggested path via the octahedral site is excluded due to its higher barrier and the rank of the saddle point. Diffusion barriers computed for H atom penetration from the surface into the inner-layers are approximately 0.54 eV (except for second-layer vacancy defects), which are all greater than the activation energy for dissociation of H2S on the Fe(1 0 0) surfaces. This suggests that H diffusion is more probable than H2S dissociation as the rate-limiting step for hydrogen permeation into the bulk Fe(1 0 0).

7501 Background: R/R ENKTL is a rare and aggressive type of non-Hodgkin’s lymphoma. Responses to chemotherapy after failure of prior asparaginase-based regimen were not durable with a median OS of < 7 months (mos) and 1-year OS rate of < 20% (Lim et al, Ann Oncol 2017; Bellei et al, Haematologica 2018). The only targeted therapy approved in China for R/R peripheral T cell lymphoma (ENKTL included) showed an ORR of 18.8% and a CR rate of 6.3% (Shi et al, Ann Oncol 2015). Here, we present the primary analysis from GEMSTONE-201, the largest registrational study reported to date to evaluate an anti-PD-L1 mAb in R/R ENKTL. Suge received breakthrough therapy designation from US FDA in 2021 for adult R/R ENKTL pts based on preliminary data of this study. Methods: Pts with ECOG PS of 0/1 and histologically confirmed ENKTL who failed prior asparaginase-based regimen were enrolled. Pts accepted suge at 1200 mg Q3W, iv, for up to 24 mos, until progression, death, or withdrawal from study. The primary endpoint was ORR (CR+PR) assessed by independent radiological review committee (IRRC) per Lugano 2014 criteria. Key secondary endpoints included investigator-assessed ORR, CR and PR rate, DoR assessed by IRRC and investigators, and safety. Results: As of the data cutoff date, Nov 10, 2021, 80 pts were enrolled and treated (median follow-up of 13.4 mos). Median age was 48 years (range 29-74); 64% were males; 74% had ECOG PS of 1 at baseline; 68% had stage IV disease; about half (49%) received ≥ 2 lines of prior systemic therapy. The median duration of treatment was 5.2 mos (range 0.7-37.4); 23 pts remained on treatment. Among the 78 evaluable pts as per IRRC, ORR was 46.2% (95% CI: 34.8%, 57.8%); 29 (37.2%) pts achieved CR; median DoR was not reached (NR); 12-mo DoR rate was 86%. Investigator’s assessments in 79 evaluable pts were consistent with IRRC results, i.e. ORR of 45.6% (95% CI: 34.3%, 57.2%), 24 (30.4%) pts with CR, and median DoR of NR. The 1- and 2-year OS rates were 68.6% and 54.6%, respectively; median OS was NR (range 0.9-37.2+ mos). Of all pts, 96% (n = 77) had at least one AE. The most common AEs were pyrexia and WBC decreased (n = 24 each, 30%). Grade ≥ 3 AEs occurred in 31 (39%) pts. Suge-related AEs occurred in 61 (76%) pts and were mostly (60%) Grade 1/2. The most common irAE assessed by sponsor was hypothyroidism (n = 13, 16%). SAEs occurred in 18 (23%) pts; 5 (6%) pts had suge-related SAEs which had all been resolved (1 with sequelae). Fatal AEs occurred in 5 (6%) pts and none were suge-related as assessed by investigators. Conclusions: Suge has demonstrated deep and durable anti-tumor activity in R/R ENKTL pts, with a high CR rate and a promising OS benefit trend comparing to historical data. Suge had a well-tolerated safety profile and no new safety signals were detected. Primary analysis indicates that suge could provide a new treatment option to R/R ENKTL pts. Clinical trial information: NCT03595657.

The Liulin Spring catchment in Shanxi Province has abundant karst groundwater resources that play a supporting role in the economic and social development of the Lvliang region. Research on the factors controlling the chemical evolution of karst groundwater can be of great significance for the sustainable utilization and effective protection of groundwater resources in the basin. In this study, the major ions of karst groundwater have been studied to identify the hydrogeochemical processes and regional evolution using 29 samples that were collected in 2014 from the recharge area, throughflow area, discharge area and stagnant area of the catchment. The results showed that the temperature and the concentrations of Na+, Ca2+, Mg2+, Cl−, HCO3− and SO42− increased with the increasing distance from the recharge area to the throughflow area, to the discharge area and then to the stagnant area. The chemical composition of karst groundwater in both recharge area and throughflow area was mainly derived from carbonate dissolution, while it was largely controlled by the weathering of silicate minerals in the discharge area, and dominated by the dissolution of both silicates and gypsum in the stagnant areas. The K+, Na+ and Cl− were mainly sourced from the dissolution of salt rock, while the Ca2+, Mg2+, HCO3−, and SO42− were mainly derived from the dissolution of calcite, dolomite, and gypsum. The hydrochemical types of karst groundwater changed from HCO3-Ca • Mg type in the recharge area to HCO3 • SO4-Ca • Mg type in the throughflow area and to HCO3 • SO4-Ca • Na • Mg type in the discharge area, and finally evolved into Cl • HCO3-Na • Ca, Cl • HCO3-Na type and Cl-Na • Ca type in the stagnant area. The results of this study will be useful to effectively guide the sustainable utilization and the integrated planning of water resources in the Liulin Spring catchment.

Multiple myeloma (MM) is still an incurable malignancy of plasma cells. Proteasome inhibitors (PIs) work as the backbone agent and have greatly improved the outcome in majority of newly diagnosed patients with myeloma. However, drug resistance remains the major obstacle causing treatment failure in clinical practice. Indirubin-3’-monoxime (Id-3) is one of the derivatives of Indirubin, a traditional Chinese medicine that has reported to be effective in the treatment of chronic myeloid leukemia and some solid tumors. In this study, we demonstrated the anti-MM activity of Id-3 in both drug sensitive and bortezomib-resistance human MM cell lines and patient-derived cells. Moreover, combination with Id-3 could sensitize MM cells to bortezomib-induced apoptosis. Mechanistically, Id-3 acts as a multifaceted regulator of cell death, which induces DNA damage and cell cycle arrest as well as abrogates NF-κB activation in MM cells. Id-3 efficiently down-regulates USP7 expression, resulting in destabilization of NEK2 and suppression of NF-κB signaling. Importantly, proteasome complex subunits PSME3 (PA28γ) and PSME4 (PA200) were down-regulated in MM cells treated with Id-3. Knockdown of PSME3 or PSME4 by shRNA caused proteasome inhibition and paraprotein accumulation, as well as sensitized MM cells to bortezomib-mediated growth arrest. Clinical data analysis demonstrated that PSME3 and PSME4 are over-expressed in relapsed/refractory MM and associated with inferior overall survival. Taken together, our study indicate that Id-3 is a novel agent triggering proteasome inhibition and represents a promising therapeutic strategy to improve patient outcome in MM. Funding: This work was supported by the Natural Science Foundation of China (8217011925, 81570181, 81920108006), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2018PT31006, 2018RC320012), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences CAMS- 2017-I2M-1-005, 2016-I2M-3-023). National Program on Key Basic Research Project 2018ZX09733003. Declaration of Interest: Dr. Kenneth. C. Anderson is the consultant: Pfizer, Amgen, Astrazeneca, Janssen, Precision Biosciences, Mana and Window. Founder/Stock Shareholder: C4 Therapeutics, Oncopep, Raqia and NextRNA. Other authors declared no competing financial interests in relation to the work described. Ethical Approval: The study was approved by the Medical Ethical Committee of the Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.