Remote Control of Energy Transformation-Based Cancer Imaging and Therapy.

Cancer treatment requires precise tumor-specific targeting at specific sites that allows for high-resolution diagnostic imaging and long-term patient-tailorable cancer therapy; while, minimizing side effects largely arising from non-targetability. This can be realized by harnessing exogenous remote stimuli, such as tissue-penetrative ultrasound, magnetic field, light, and radiation, that enable local activation for cancer imaging and therapy in deep tumors. A myriad of nanomedicines can be efficiently activated when the energy of such remote stimuli can be transformed into another type of energy. This review discusses the remote control of energy transformation for targetable, efficient, and long-term cancer imaging and therapy. Such ultrasonic, magnetic, photonic, radiative, and radioactive energy can be transformed into mechanical, thermal, chemical, and radiative energy to enable a variety of cancer imaging and treatment modalities. The current review article describes multimodal energy transformation where a serial cascade or multiple types of energy transformation occur. This review includes not only mechanical, chemical, hyperthermia, and radiation therapy but also emerging thermoelectric, pyroelectric, and piezoelectric therapies for cancer treatment. It also illustrates ultrasound, magnetic resonance, fluorescence, computed tomography, photoluminescence, and photoacoustic imaging-guided cancer therapies. It highlights afterglow imaging that can eliminate autofluorescence for sustained signal emission after the excitation.

Endowing Metal-Organic Coordination Materials with Chiroptical Activity by a Chiral Anion Strategy.

Recently, chiral metal-organic coordination materials have emerged as promising candidates for a wide range of applications in chiroptoelectronics, chiral catalysis, and information encryption, etc. Notably, the chiroptical effect of coordination chromophores makes them appealing for applications such as photodetectors, OLEDs, 3D displays, and bioimaging. The direct synthesis of chiral coordination materials using chiral organic ligands or complexes with metal-centered chirality is very often tedious and costly. In the case of ionic coordination materials, the combination of chiral anions with cationic, achiral coordination compounds through noncovalent interactions may endow molecular materials with desirable chiroptical properties. The use of such a simple chiral strategy has been proven effective in inducing promising circular dichroism and/or circularly polarized luminescence signals. This concept article mainly delves into the latest advances in exploring the efficacy of such a chiral anion strategy for transforming achiral coordination materials into chromophores with superb photo- or electro-chiroptical properties. In particular, ionic small-molecular metal complexes, metal clusters, coordination supramolecular assemblies, and metal-organic frameworks containing chiral anions are discussed. A perspective on the future opportunities on the preparation of chiroptical materials with the chiral anion strategy is also presented.

Digital inverse patterning solutions for fabrication of high-fidelity microstructures in spatial light modulator (SLM)-based projection lithography.

Digital mask projection lithography (DMPL) technology is gaining significant attention due to its characteristics of free-mask, flexibility, and low cost. However, when dealing with target layouts featuring sizes smaller than the wavelength scale, accurately producing resist patterns that closely match the target layout using conventional methods to design the modulation coefficients of digital masks produced by spatial light modulators (SLM) becomes challenging. Here, we present digital inversion lithography technology (DILT), which offers what we believe to be a novel approach to reverse engineer the modulation coefficients of digital masks. In the case of binary amplitude modulation, DILT achieves a remarkable reduction in pattern errors (PE), reaching the original 0.26. At the same time, in the case of the gray amplitude modulation, the PE can be reduced to the original 0.05, which greatly improves the high-fidelity transfer of the target layout. This significant improvement enhances the accuracy of target design transfer. By leveraging the capabilities of DILT, DMPL can now attain higher precision and reliability, paving the way for more advanced applications in the field of micro-nano device manufacturing.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.

Evidence from a meta-analysis and systematic review reveals the global prevalence of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) is a preclinical and transitional stage between healthy ageing and dementia. The purpose of our study was to investigate the recent pooled global prevalence of MCI. Methods: This meta-analysis was in line with the recommendations of Cochrane's Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. We conducted a comprehensive search using the PubMed, Embase, Web of Science, CNKI, WFD, VIP, and CBM from their inception to March 1, 2023. Quality assessment was guided by the Agency for Healthcare Research and Quality (AHRQ) methodology checklist. The pooled global prevalence of MCI was synthesized using meta-analysis via random effect model. Subgroup analyses were performed to examine considered factors potentially associated with MCI prevalence. Results: We identified 233 studies involving 676,974 individuals aged above 50 years. All the studies rated as moderated-to-high quality. The overall prevalence of MCI was 19.7% [95% confidence interval (95% CI): 18.3-21.1%]. Subgroup analyses revealed that the global prevalence of MCI increased over time, with a significant rise [32.1% (95% CI: 22.6-41.6%)] after 2019. Additionally, MCI prevalence in hospitals [34.0% (95% CI: 22.2-45.7%)] was higher than in nursing homes [22.6% (95% CI: 15.5-29.8%)] and communities [17.9% (95% CI: 16.6-19.2%)], particularly after the epidemic of coronavirus disease 2019 (COVID-19). Conclusion: The global prevalence of MCI was 19.7% and mainly correlated with beginning year of survey and sample source. The MCI prevalence increased largely in hospitals after 2019 may be related to the outbreak of COVID-19. Further attention to MCI is necessary in the future to inform allocation of health resources for at-risk populations.

Comparing genomes of Fructus Amomi-producing species reveals genetic basis of volatile terpenoid divergence.

Wurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are 2 primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoid divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contributes to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae.

Generating an M2 × N2 spot array with a dual-period hybrid Dammann grating fabricated using maskless projection lithography.

The Dammann grating (DG), which redistributes a collimated laser beam into a spot array with a uniform intensity, is a widely adopted approach for profile measurement. Conventional DGs for dense spot projection are binary phase gratings with precisely designed groove structures, which suffer from low efficiency, poor uniformity, and a hard-to-fabricate fine feature size when utilized for a large field of view (FOV). Here, we propose a new, to the best of our knowledge, hybrid DG architecture consisting of two different grating periods which effectively generates an engineering M2 × N2 spot array with a non-complex structural design. As a proof-of-concept, a dual-period hybrid DG with a two-scale grating period ratio of 11.88 µm/95.04 µm (∼1/8) is designed and fabricated as a means to generate a dense 72 × 72 diffraction spot array with a FOV of 17° × 17°. In addition, the DG exhibits superior performance, with a high efficiency (>60%) and a low non-uniformity (<18%) at a wavelength of 532 nm. This kind of hybrid DG constructed from photoresist patterns with a minimum feature size of ∼1.2 µm can be perfectly fabricated by maskless projection lithography for large-scale and low-cost production. The proposed dual-period hybrid DG can pave the way for depth-perception-related applications such as face unlocking and motion sensing.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation: A Retrospective Study.

OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.

Experimental Examination of Entanglement Estimates.

Recently, a proper genuine multipartite entanglement measure has been found for three-qubit pure states [see Xie and Eberly, Phys. Rev. Lett. 127, 040403 (2021)PRLTAO0031-900710.1103/PhysRevLett.127.040403], but capturing useful entanglement measures for mixed states has remained an open challenge. So far, it requires not only a full tomography in experiments, but also huge calculational labor. A leading proposal was made by Gühne, Reimpell, and Werner [Phys. Rev. Lett. 98, 110502 (2007)PRLTAO0031-900710.1103/PhysRevLett.98.110502], who used expectation values of entanglement witnesses to describe a lower bound estimation of entanglement. We provide here an extension that also gives genuine upper bounds of entanglement. This advance requires only the expectation value of any Hermitian operator. Moreover, we identify a class of operators A_{1} that not only give good estimates, but also require a remarkably small number of experimental measurements. In this Letter, we define our approach and illustrate it by estimating entanglement measures for a number of pure and mixed states prepared in our recent experiments.

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

OBJECTIVE: We aimed to identify new, more accurate risk factors of liver transplantation for liver cancer through using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Using the SEER database, we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma (HCC) and subsequent liver transplantation between 2010 and 2017. Overall survival (OS) was estimated using Kaplan-Meier plotter. Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease [presented as adjusted hazard ratios (HR) with 95% CIs]. RESULTS: Totally, 1530 eligible patients were included in the analysis. There were significant differences in ethnicity (P=0.04), cancer stage (P<0.001), vascular invasion (P<0.001) and gall bladder involvement (P<0.001) between the groups that survived, died due to cancer, or died due to other causes. In the Cox regression model, there were no significant differences in OS at 5 years with different operative strategies (autotransplantation versus allotransplantation), nor at survival at 1 year with neoadjuvant radiotherapy. However, neoadjuvant radiotherapy did appear to improve survival at both 3 years (HR: 0.540, 95% CI: 0.326-0.896, P=0.017) and 5 years (HR: 0.338, 95% CI: 0.153-0.747, P=0.007) from diagnosis. CONCLUSION: This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC. These criteria can be used to inform patient selection and consent in this setting. Preoperative radiotherapy may improve long-term survival post-transplantation.

[Effect of acupuncture at Weizhong (BL 40) on bladder urination function based on ultrasound].

OBJECTIVE: To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function. METHODS: A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi. In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi. The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups. RESULTS: After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture (P<0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group (P<0.05, P<0.01). CONCLUSION: Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang-fu organs.

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects.

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.

[Chemical constituents in different parts of Ixeris sonchifolia based on UPLC-LTQ-Orbitrap-MS~n].

The chemical constituents in stem leaf, root, and flower of Ixeris sonchifolia were identified by the ultra performance li-quid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS~n). The separation was performed on an Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) with a mobile phase of water(containing 0.1% formic acid, A)-acetonitrile(B) with gradient elution. With electrospray ionization source, the data of 70% methanol extract from stem leaf, root and flower of I. sonchifolia were collected by high-resolution full-scan Fourier transform spectroscopy, data dependent acquisition, precursor ion scan, and selected ion monitoring in the negative and positive ion modes. The compounds were identified based on accurate molecular weight, retention time, fragment ions, comparison with reference standard, Clog P and references. A total of 131 compounds were identified from the 70% methanol extract of I. sonchifolia, including nucleosides, flavonoids, organic acids, terpenoids, and phenylpropanoids, and 119, 110, and 126 compounds were identified from the stem leaf, root and flower of I. sonchifolia, respectively. In addition, isorhamnetin, isorhamnetin-7-O-sambubioside and caffeylshikimic acid were discovered from I. sonchifolia for the first time. This study comprehensively analyzed and compared the chemical constituents in different parts of I. sonchifolia, which facilitated the discovery of effective substances and the development and application of medicinal material resources of I. sonchifolia.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Structural and Energetic Origin of Different Product Specificities and Activities for SETD3 and Its Mutants on the Methylation of the ß-Actin H73K Peptide: Insights from a QM/MM Study.

The methylation of the lysine residue can affect some fundamental biological processes, and specific biological effects of the methylations are often related to product specificity of methyltransferases. The question remains concerning how active-site structural features and dynamics control the activity as well as the number (1, 2, or 3) of methyl groups on methyl lysine products. SET domain containing protein 3 (SETD3) has been identified recently as the ß-actin histidine73-N3 methyltransferase, and also, it has a weak methylation activity on the H73K ß-actin peptide for which the target H73 residue is mutated into K73. Interestingly, the K73 methylation activity of SETD3 increases significantly as a result of the N255 → A or N255 → F/W273 → A mutation, and the N255A product specificity also differs from that of wild-type. Here, we performed QM/MM molecular dynamics and potential of mean force (PMF) simulations for SETD3 and its mutants (N255A and N255F/W273A) to study how SETD3 and its mutants could have different product specificities and activities for the K73 methylation. The PMF simulations show that the barrier for the first methylation of K73 is higher compared to the barrier of the H73 methylation in SETD3. Moreover, the second methylation of K73 has been found to have a barrier from the free energy simulation that is higher by 2.2 kcal/mol compared to the barrier of the first methyl transfer to K73, agreeing with the suggestion that SETD3 is a monomethylase. For the first, second, and third methylations of K73 in the N255A mutant, the barriers obtained from the PMF simulations for transferring the second and third methyl groups are found to be lower relative to the barrier for the first methyl transfer. Thus, N255A can be considered as a trimethyl lysine methyltransferase. In addition, for the first K73 methylation, the activities from the PMF simulations follow the order of N255F/W273A > N255A > WT, in agreement with experiments. The examination of the structural and dynamic results at the active sites provides better understanding of different product specificities and activities for the K73 methylations in SETD3 and its mutants. It is demonstrated that the existence of well-balanced interactions at the active site leading to the near attack conformation is of crucial importance for the efficient methyl transfers. Moreover, the presence of potential interactions (e.g., the C-H···O and cation-π interactions) that are strengthening at the transition state can also be important. Furthermore, the activity as well as product specificity of the K73 methylation also seems to be controlled by certain active-site water molecules which may be released to provide extra space for the addition of more methyl groups on K73.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Efficacy of Drpitor1a, a Dynamin-Related Protein 1 inhibitor, in Pulmonary Arterial Hypertension.

Rationale: Dynamin-related protein 1 (Drp1), a large GTPase, mediates mitochondrial fission. Increased Drp1-mediated fission permits accelerated mitosis, contributing to hyperproliferation of pulmonary artery smooth muscle cells (PASMC), which characterizes pulmonary arterial hypertension (PAH). We developed a Drp1 inhibitor, Drpitor1a, and tested its ability to regress PAH. Objectives: Assess Drpitor1a's efficacy and toxicity in: a)normal and PAH human PASMC (hPASMC); b)normal rats versus rats with established monocrotaline (MCT)-induced PAH. Methods: Drpitor1a's effects on recombinant and endogenous Drp1-GTPase activity, mitochondrial fission, and cell proliferation were studied in hPASMCs (normal=3; PAH=5). Drpitor1a's pharmacokinetics and tissue concentrations were measured (n=3 rats/sex). In a pilot study (n=3-4/sex/dose), Drpitor1a (1mg/kg/48-hours, intravenous) reduced adverse PA remodeling only in females. Consequently, we compared Drpitor1a to vehicle in normal (n=6 versus 8) and MCT-PAH (n=9 and 11) females, respectively. Drpitor1a treatment began 17-days post-MCT with echocardiography and cardiac catheterization performed 28-29 days post-MCT. Results: Drpitor1a inhibited recombinant and endogenous Drp1 GTPase activity, which was increased in PAH hPASMC. Drpitor1a inhibited mitochondrial fission and proliferation and induced apoptosis, in PAH hPASMC but not normal hPASMC. Drpitor1a tissue levels were higher in female versus male RVs. In MCT-PAH females, Drpitor1a regressed PA obstruction, lowered pulmonary vascular resistance, and improved RV function, without hematologic, renal, or hepatic toxicity. Conclusions: Drpitor1a inhibits Drp1 GTPase, reduces mitochondrial fission, and inhibits cell proliferation in PAH hPASMC. Drpitor1a caused no toxicity in MCT-PAH and had no significant effect on normal rats or hPASMCs. Drpitor1a is a potential PAH therapeutic which displays an interesting therapeutic sexual dimorphism.

Label-free neural networks-based inverse lithography technology.

Neural network-based inverse lithography technology (NNILT) has been used to improve the computational efficiency of large-scale mask optimization for advanced photolithography. NNILT is now mostly based on labels, and its performance is affected by the quality of labels. It is difficult for NNILT to achieve high performance and extrapolation ability for mask optimization without using labels. Here, we propose a label-free NNILT (LF-NNILT), which is implemented completely without labels and greatly improves the printability of the target layouts and the manufacturability of the synthesized masks compared to the traditional ILT. More importantly, the optimization speed of LF-NNILT is two orders of magnitude faster than the traditional ILT. Furthermore, LF-NNILT is simpler to implement and can achieve better solvers to support the development of advanced lithography.