A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder.

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression.

Saturable absorption properties and ultrafast photonics applications of HfS3.

In this Letter, we focus on investigating the ultrafast photonics applications of two-layer HfS3 nanosheets. We prepared two-layer HfS3 nanosheets and carried out experiments to study their nonlinear saturable absorption properties. The results showed that the two-layer HfS3-based saturable absorber exhibited a modulation depth of 16.8%. Additionally, we conducted theoretical calculations using first principles to estimate the structural and electronic band properties of the two-layer HfS3 material. Furthermore, we utilized the two-layer HfS3 materials as SAs in an erbium-doped fiber cavity to generate mode-locked laser pulses. We measured a repetition frequency of 8.74 MHz, a pulse duration of 540 fs, and a signal-to-noise ratio of 77 dB. Overall, our findings demonstrate that the two-layer HfS3 material can serve as a reliable saturable absorber, possessing properties comparable to currently used two-dimensional materials. This expands the application fields of HfS3 materials and highlights their potential for advanced optoelectronic devices.

Engineered platelet-based immune engager for tumor post-surgery treatment.

Tumor metastasis and recurrence are principal reasons for the high mortality and poor prognosis of cancers. Inefficient engagement between T cell and tumor cell, as well as the universal existence of immune checkpoints, are important factors to the limited immunological surveillance of the immune systems to tumor cells. Herein, an immune engager based on engineered platelets with CD3 antibody modification (P-aCD3) was constructed to facilitate the contact between T cell and tumor cell via providing the anchoring sites of above two cells. Combined with the immune checkpoint blockade strategy, P-aCD3 effectively enhanced T cell mediated cytotoxicity and inhibited tumor recurrence and metastasis in mice melanoma postoperative model and breast cancer model, resulting in significantly prolonged survival of mice.

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination.

Chemoimmunotherapy is a promising strategy in tumor treatments. In this study, immunogenic dead cells were engineered by the sequential treatment of live tumor cells with ultraviolet (UV) irradiation and cryo-shocking. The dead cells could serve as a lung-targeting vehicle and tumor vaccine after differential loading of the chemo-drug 10-hydroxycamptothecin (HCPT) and immune adjuvant Quillaja saponin-21 (QS-21) via physical absorption and chemical conjugation, respectively. After intravenous administration, the dead cells could be trapped in pulmonary capillaries and could fast release HCPT to enhance the drug accumulation in local tissues. Further, the immunogenic dead cells elicited antitumor immune responses together with the conjugated adjuvant QS-21 to achieve the elimination and long-term surveillance of tumor cells. In a lung tumor-bearing mice model, this drug-delivery system achieved synergistic antitumor efficacy and prolonged the survival of mice.

Immunosuppressive dead cell as lung-targeting vehicle and cytokine absorption material for cytokine storm attenuation of pneumonia.

Effectively controlling cytokine storm is important to reduce the mortality of severe pneumonia. In this work a bio-functional dead cell was engineered by one-time quick shock of live immune cells in liquid nitrogen, and the obtained immunosuppressive dead cell could server as both lung-targeting vehicle and cytokine absorption material. After loading the anti-inflammatory drugs of dexamethasone (DEX) and baicalin (BAI), the drug-loaded dead cell (DEX&BAI/Dead cell) could first passively target to the lung after intravenous administration and quickly release the drugs under high shearing stress of pulmonary capillaries, realizing drug enrichment in the lung. Then, the immunosuppressive dead cell acted as the camouflage of normal immune cells with various cytokine receptors exposing on their surface, to "capture" the cytokines and further reduce the state of inflammation. With above formulation design, a synergic anti-inflammatory effect between drugs and carrier could be achieved. In a lipopolysaccharide-induced pneumonia mice model, this system could calm down the cytokine storm with high efficacy and elongate the survival of mice.

Chromium oxide film for Q-switched and mode-locked pulse generation.

Chromium oxide (Cr2O3) is a promising material used in the applications such as photoelectrochemical devices, photocatalysis, magnetic random access memory, and gas sensors. But, its nonlinear optical characteristics and applications in ultrafast optics have not been studied yet. This study prepares a microfiber decorated with a Cr2O3 film via magnetron sputtering deposition and examines its nonlinear optical characteristics. The modulation depth and saturation intensity of this device are determined as 12.52% and 0.0176 MW/cm2. Meanwhile, the Cr2O3-microfiber is applied as a saturable absorber in an Er-doped fiber laser, and stable Q-switching and mode-locking laser pulses are successfully generated. In the Q-switched working state, the highest output power and shortest pulse width are measured as 12.8 mW and 1.385 µs, respectively. The pulse duration of this mode-locked fiber laser is as short as 334 fs, and its signal-to-noise ratio is 65 dB. As far as we know, this is the first illustration of using Cr2O3 in ultrafast photonics. The results confirm that Cr2O3 is a promising saturable absorber material and significantly extend the scope of saturable absorber materials for innovative fiber laser technologies.

Characteristics of the paravertebral muscle in adult degenerative scoliosis with PI-LL match or mismatch and risk factors for PI-LL mismatch.

Objective: Pelvic incidence (PI) minus the lumbar lordosis (LL) angle (PI-LL) correlates with function and disability. It is associated with paravertebral muscle (PVM) degeneration and is a valuable tool for surgical planning of adult degenerative scoliosis (ADS). This study aims to explore the characteristics of PVM in ADS with PI-LL match or mismatch and to identify the risk factors for PI-LL mismatch. Methods: A total of 67 patients with ADS were divided into PI-LL match and mismatch groups. The visual analog scale (VAS), symptom duration, and Oswestry disability index (ODI) were used to assess patients' clinical symptoms and quality of life. The percentage of fat infiltration area (FIA%) of the multifidus muscle at the L1-S1 disc level was measured by using MRI with Image-J software. Sagittal vertical axis, LL, pelvic tilt (PT), PI, sacral slope, and the asymmetric and average degeneration degree of the multifidus were recorded. Logistic regression analysis was done to identify the risk factors for PI-LL mismatch. Results: In the PI-LL match and mismatch groups, the average FIA% of the multifidus on the convex side was less than that on the concave side (P < 0.05). There was no statistical difference of asymmetric degeneration degree of the multifidus between the two groups (P > 0.05). In the PI-LL mismatch group, the average degeneration degree of the multifidus, VAS, symptom duration, and ODI were significantly higher than that in the PI-LL match group, respectively (32.22 ± 6.98 vs. 26.28 ± 6.23 (%), 4.33 ± 1.60 vs. 3.52 ± 1.46, 10.81 ± 4.83 vs. 6.58 ± 4.23 (month), 21.06 ± 12.58 vs. 12.97 ± 6.49, P < 0.05). The average degeneration degree of the multifidus muscle was positively correlated with the VAS, symptom duration, and ODI, respectively (r = 0.515, 0.614, and 0.548, P < 0.05). Sagittal plane balance, LL, PT, and the average degeneration degree of the multifidus were the risk factors for PI-LL mismatch (OR: 15.447, 95% CI: 1.274-187.269; OR: 0.001, 95% CI: 0.000-0.099; OR: 107.540, 95% CI: 5.195-2,225.975; OR: 52.531, 95% CI: 1.797-1,535.551, P < 0.05). Conclusion: The PVM on the concave side was larger than that on the convex side in ADS irrespective of whether PI-LL matched or not. PI-LL mismatch could aggravate this abnormal change, which is an important cause of pain and disability in ADS. Sagittal plane imbalance, decreased LL, higher PT, and larger average degeneration degree of the multifidus were independent risk factors for PI-LL mismatch.

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.

Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat model of chronic unpredictable stress.

INTRODUCTION: There is an unmet need for better nonpharmaceutical treatments for depression. Low-intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. OBJECTIVE: The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. METHODS: Chronic unpredictable stress (CUS) was used to generate rats with depression-like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression-like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin-eosin and Nissl staining. RESULTS: Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. CONCLUSIONS: Chronic LIPUS stimulation can effectively and safely improve depression-like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression.

Stability and Sensing Enhancement by Nanocubic CeO2 with {100} Polar Facets on Graphene for NO2 at Room Temperature.

Metal oxides with a polar surface interact strongly with polar NO2 molecules, thus facilitating sensitive detection of NO2. In this work, the composites comprising graphene and cubic CeO2 nanoparticles with the {100} polar surface are prepared by a hydrothermal technique, and they exhibit fast response, excellent selectivity, stable recovery, and sensitive detection with a low detection limitation of 1 ppm for NO2 at room temperature. According to the first-principle calculations, the adsorption energy of NO2 on the CeO2{100} polar surface is the most negative corresponding to the strongest interactions between them. The formation energy of oxygen vacancies (Ov) on the {100} polar plane is also negative, and the abundant Ov facilitates the adsorption of NO2. The internal electric field near the polar surface promotes the charge separation and accelerates the charge exchange between NO2 and the composites. In addition, graphene promotes electron transfer at the interface and improves the stability of the CeO2{100} polar surface. The composites of graphene and metal oxides with a polar surface are excellent for NO2 detection, and the discovery reveals a new sensing strategy.

Abnormal change of paravertebral muscle in adult degenerative scoliosis and its association with bony structural parameters.

PURPOSE: While many studies have explored the association between paravertebral muscle (PVM) change and low back pain/lumbar spinal stenosis, little is known about PVM change in adult degenerative scoliosis (ADS). The present study explored the PVM change in ADS and investigated its association with bony structural parameters. METHODS: We evaluated 78 patients in ADS without radiculopathy (ADS group) and 65 healthy persons without degenerative lumbar diseases (control group). Percentage of fat infiltration area (%FIA) of multifidus muscle at L1 to S1 disk level was measured by MRI, using ImageJ software. Lumbar scoliosis Cobb's angle, lumbar lordotic angle, lateral vertebral translation, and apical vertebral rotation were recorded in ADS group, and relationship between PVM change and these factors was analyzed. RESULTS: In the control group, the mean %FIA of multifidus muscle was not significantly different between the bilateral sides at all levels (P > 0.05). In the ADS group, the mean %FIA was significantly higher on the concave side than the convex side at all levels (P < 0.05). Asymmetric degree of multifidus muscle change was 8.55% ± 4.91%, which was positively correlated with lumbar scoliosis Cobb's angle, lateral vertebral translation, and apical vertebral rotation (0 < r < 1, P < 0.05), but negatively weak-correlated with lumbar lordotic angle (- 1 < r < 0, P < 0.05). CONCLUSIONS: Asymmetric PVM change in ADS is more often seen on the concave side, which is positive to evaluate the progression of scoliosis. Its asymmetric degree increases with progression of lumbar scoliosis Cobb's angle and decreased lumbar lordotic angle. Apical vertebral rotation and lateral vertebral translation can aggravate the asymmetric degree.