Promoting H2 generation of BiFeO3 photocathodes by a catalyst-sensitizer dyad linked with Sn(dipicolinate)2.

An innovative method for the fabrication of a catalyst-sensitizer dyad-based photoelectrode was developed by using the coordinated interaction between the pyridine-2,6-dicarboxylic group and Sn4+. A dyad (C1 + PDI) was loaded on the mesoporous BiFeO3 (BFO) photocathode for light-driven H2 generation. The dyad could expand the light absorption range and promote the surface charge separation of BFO, resulting in an enhanced photocurrent.

Identification of a cis-element for long glandular trichome-specific gene expression, which is targeted by a HD-ZIP IV protein.

Glandular trichomes are epidermal outgrowths that secret a variety of secondary metabolites, which not only help plants adapt to environmental stresses but also have important commercial value in fragrances, pharmaceuticals, and pesticides. In Nicotiana tabacum, it has been confirmed that a B-type cyclin, CycB2, negatively regulates the formation of long glandular trichomes (LGTs). This study aimed to identify the upstream regulatory gene involved in LGT formation by screening LGT-specific cis-elements within the NtCycB2 promoter. Using GUS as a reporter gene, the tissue-driven ability of NtCycB2 promoter showed that NtCycB2 promoter could drive GUS expression specifically in LGTs. Function analysis of a series of successive 5' truncations and synthetic segments of the NtCycB2 promoter indicated that the 87-bp region from -1221 to -1134 of the NtCycB2 promoter was required for gene expression in LGTs, and the L1-element (5'-AAAATTAATAAGAG-3') located in the 87-bp region contributed to the gene expression in the stalk of LGTs. Further Y1H and LUC assays confirmed that this L1-element exclusively binds to a HD-Zip IV protein, NtHD13. Gene function analysis revealed that NtHD13 positively controlled LGT formation, as overexpression of NtHD13 resulted in a high number of LGTs, whereas knockout of NtHD13 led to a decrease in LGTs. These findings demonstrate that NtHD13 can bind to an L1-element within the NtCycB2 promoter to regulate LGT formation.

Diagnostic Stability in Psychiatric Patients From Hospital Admission to Discharge: A 10-Year Retrospective Study.

OBJECTIVE: This study aimed to evaluate the consistency or stability of mental disorders diagnosed in the psychiatry ward setting, investigate factors associated with consistency, and observe the disease distribution over the decade. METHODS: A total of 20,359 psychiatric inpatients were included in this retrospective study from June 2011 to December 2020. Diagnoses from the first admission to discharge were evaluated to determine the diagnostic consistency during hospitalization. Readmissions were selected as the subgroup, whose first and last discharge diagnoses were compared to analyze the relatively long-term diagnostic stability. Demographic and clinical characteristics were collected to identify predictors of diagnostic discrepancy. RESULTS: From 2011-2020, the hospitalization rate decreased from 42.7% to 20.7% for schizophrenia and grew from 13.3% to 23.8% for depression. Diagnoses were retained by 92.6% of patients at their first discharge diagnosis, ranging from 100% for disorders of psychological development to 16.3% for unspecified mental disorders. About 33.9% of diagnostic conversions were to bipolar disorder in patients having inconsistent diagnoses. However, among rehospitalizations, the diagnostic stability notably dropped to 71.3%. For rehospitalizations, mood disorders and schizophrenia spectrum disorders were relatively stable diagnoses categories, with 72.6% to 76.7% of patients receiving the same diagnosis, although results of specified diagnoses within these categories ranged from 5.9% to 91.0%. Except for mood disorders and schizophrenia spectrum disorders, the diagnoses of all other categories were below 70%. Long lengths of hospitalization and old age were associated with short-term diagnosis alterations. CONCLUSION: Longitudinal follow-up and integration of multiple aspects of information are essential for accurate diagnosis.

Novel molecular photosensitizer with simultaneously GSH depletion, aggregation inhibition and accelerated elimination for improved and safe photodynamic therapy.

The major challenges in photodynamic therapy (PDT) are the neutralization of cytotoxic reactive oxygen species (ROS) by the excessive antioxidant glutathione (GSH) in tumor cells, high self-aggregation of most photosensitizers (PSs), and long time to protect from light after treatment. Thus, to develop the molecular PSs for the improved and safe PDT in clinic, a novel and versatile PS (Mal-Pc) has been designed by di-substituting maleimides to the axial positions of silicon (Ⅳ) phthalocyanine. Owning to the conjugation of maleimides, Mal-Pc can not only entry tumor cells more easily and faster, but also can react with the intracellular overexpressed GSH after entry. In addition, upon electrophilic reaction with GSH, the inhibition of self-aggregation of Mal-Pc has been demonstrated by the restoration of the fluorescence emission in aqueous media. As a result, the intracellular ROS levels and photocytotoxicity of Mal-Pc are dramatically enhanced. Finally, the high hydrophilicity of the product GS-conjugates facilitates Mal-Pc eliminate from the normal cells more rapidly. Overall, this work revealed the high potential of the versatile molecular Mal-Pc for highly efficient and safe PDT in clinical translation.

A MCL-1-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy, sensitization to ROS-induced damage, and immune response.

As growth factor receptor-2 (HER-2), progesterone receptor (PR) and estrogen receptor (ER) are scarce in triple-negative breast cancer (TNBC), it is a great challenge to combat TNBC with high tumor specificity and therapeutic efficacy. Most traditional treatments including surgical resection, chemotherapy, and radiotherapy would more or less cause serious side effects and drug resistance. Photodynamic therapy (PDT) has huge potential in the treatment of TNBC for minimal invasiveness, low toxicity, less drug resistance and high spatiotemporal selectivity. Inspired by the advantages of small-molecule-targeted PDT and the sensitization effect of myeloid cell leukemia-1 (MCL-1) inhibitor, a novel photosensitizer BC-Pc was designed by conjugating MCL-1 inhibitor with zinc phthalocyanines. Owning to 3-chloro-6-methyl-1-benzothiophene-2-carboxylic acid (BC) moiety, BC-Pc exhibits the high affinity towards MCL-1 and reduce its self-aggregation in TNBC cells. Therefore, MCL-1 targeted BC-Pc showed remarkable intracellular fluorescence and ROS generation in TNBC cells. Additionally, BC-Pc can selectively sensitize TNBC cells to ROS-induced damage, resulting in improved therapeutic effect to TNBC cells and negligible toxicity to normal cells. More importantly, BC-Pc can effectively inhibit the migration and invasion of TNBC cells, and enhance immune response, all of which will be beneficial to eradicate TNBC. To the best of our knowledge, BC-Pc is the novel MCL-targeted photosensitizer, which owns the amplified ROS-induced lethality and anticancer immune response for TNBC. Overall, our study provides a promising strategy to achieve targeting and highly efficient therapy of TNBC.

Overlapping and segregated changes of functional hubs in melancholic depression and non-melancholic depression.

BACKGROUND: Previous research found associations between neuropsychiatric disorders and patterns of highly connected "hub" nodes, which are crucial in coordinating brain functions. Melancholic depression is considered a relatively distinct and homogenous subtype of major depressive disorder (MDD), which responds better to pharmacological treatments than placebos or psychotherapies. Accordingly, melancholic depression probably has distinct neuropathological underpinnings. This study aims to examine the overlapping and segregated changes of functional hubs in melancholic and non-melancholic MDD. METHODS: Thirty-one melancholic patients, 28 non-melancholic patients, and 32 healthy controls were included. Resting-state functional imaging data were analyzed using global functional connectivity. RESULTS: Both melancholic and non-melancholic patients had increased GFC in the bilateral insula and decreased GFC in the PCC/precuneus compared to HCs. The distinction was that melancholic patients showed increased GFC in the bilateral thalamus, right inferior parietal lobule (IPL), and left cerebellum Crus I and decreased GFC in the left temporal lobe, whereas non-melancholic patients showed increased GFC in the left superior parietal lobe. Additionally, compared with non-melancholic patients, melancholic individuals displayed significant increases of GFC in the left IPL and cerebellum. CONCLUSION: Increased GFC of the insula and decreased GFC of the PCC and precuneus are the common abnormalities of melancholic and non-melancholic MDD. Hyperconnectivity of the IPL and cerebellum might be distinctive neuropathological features of melancholic MDD.

A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response.

Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive oxygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and invasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.

Multiple-Network Alterations in Major Depressive Disorder With Gastrointestinal Symptoms at Rest Revealed by Global Functional Connectivity Analysis.

Objective: Gastrointestinal (GI) symptoms are prominent in major depressive disorder (MDD) and bring patients lots of complaints and troubles. We aimed to explore whether there were some distinctive brain image alterations in MDD with GI symptoms, which could be used to distinguish MDD with GI symptoms from those without GI symptoms and healthy controls (HCs). Methods: A total of 35 outpatients with GI symptoms, 17 outpatients without GI symptoms, and 28 HCs were recruited. All the participants were scanned by a resting-state functional magnetic resonance imaging. Imaging data were analyzed with the global functional connectivity (GFC) and support vector machine methods. Results: MDD with GI symptoms showed decreased GFC in the left superior medial prefrontal cortex (MPFC) compared with MDD without GI symptoms. Compared with HCs, MDD with GI symptoms showed decreased GFC in the bilateral middle temporal pole (MTP) and left posterior cingulate cortex/precuneus (PCC/Pcu), and increased GFC in the right insula and bilateral thalamus. SVM analysis showed that an accuracy was 78.85% in differentiating MDD with GI symptoms from MDD without GI symptoms by using the GFC of the left superior MPFC. A combination of GFC of the left PCC/Pcu and bilateral MTP exhibited the highest accuracy (87.30%) in differentiating patients with MDD with GI symptoms from HCs. Conclusion: MDD with GI symptoms showed abnormal GFC in multiple networks, including the default mode network and cortico-limbic mood-regulating circuit. Using abnormal GFC might work well to discriminate MDD with GI symptoms from MDD without GI symptoms and HCs.

Abnormal Default Mode Network Homogeneity in Major Depressive Disorder With Gastrointestinal Symptoms at Rest.

Background: Gastrointestinal (GI) symptoms are prominent in many patients with major depressive disorder (MDD). However, it remains unclear whether MDD patients with GI symptoms have brain imaging alterations in the default mode network (DMN) regions. Methods: A total of 35 MDD patients with GI symptoms, 17 MDD patients without GI symptoms, and 28 healthy controls (HCs) were recruited. All participants underwent resting-state functional magnetic resonance imaging scans. Network homogeneity (NH) and support vector machine (SVM) methods were used to analyze the imaging data. Results: Gastrointestinal group showed higher 17-item Hamilton Rating Scale for Depression total scores and factor scores than the non-GI group. Compared with the non-GI group and HCs, the GI group showed decreased NH in the right middle temporal gyrus (MTG) and increased NH in the right precuneus (PCu). The SVM results showed that a combination of NH values of the right PCu and the right MTG exhibited the highest accuracy of 88.46% (46/52) to discriminate MDD patients with GI symptoms from those without GI symptoms. Conclusion: Major depressive disorder patients with GI symptoms have more severe depressive symptoms than those without GI symptoms. Distinctive NH patterns in the DMN exist in MDD patients with GI symptoms, which can be applied as a potential brain imaging marker to discriminate MDD patients with GI symptoms from those without GI symptoms.

Disrupted Cerebellar-Default Mode Network Functional Connectivity in Major Depressive Disorder With Gastrointestinal Symptoms.

Gastrointestinal (GI) symptoms are one of the common somatic symptoms presented in patients with major depressive disorder (MDD). Higher frequency of GI symptoms and higher GI symptom burden were linked to greater depression severity and increased risk of suicide ideation. However, few studies have explored the underlying mechanisms of GI symptoms in MDD. Based on previous studies, the cerebellar-DMN circuits may play a potentially critical role in GI symptoms comorbid with depression. Fifty-two first-episode drug-naive patients with MDD (35 with GI symptoms and 17 without GI symptoms) and 28 matched healthy controls were recruited in the current study and underwent resting-state functional magnetic resonance imaging scan. Cerebellar seed-based functional connectivity maps were established. Relative to depressed patients without GI symptoms, significantly increased cerebellar-anterior default mode network (DMN) connectivities were found in those with GI symptoms. Both increased and decreased functional connectivities were found between cerebellum and posterior DMN in patients with GI symptoms compared with those without GI symptoms and healthy controls. Moreover, the right Crus I - right superior temporal gyrus connectivity value was related to severity of GI symptoms and depression in all patients with MDD. The support vector machine analysis demonstrated a satisfactory classification accuracy (89%) of the disrupted cerebellar-DMN connectivities for correctly identifying MDD patients with GI symptoms. These results revealed the possible neural mechanisms for the involvement of cerebellar-DMN circuits in GI symptoms co-occurred with MDD.

Shared and Distinct Fractional Amplitude of Low-Frequency Fluctuation Patterns in Major Depressive Disorders With and Without Gastrointestinal Symptoms.

Objective: Gastrointestinal (GI) symptoms are fairly common somatic symptoms in depressed patients. The purpose of this study was to explore the influence of concomitant GI symptoms on the fractional amplitude of low-frequency fluctuation (fALFF) patterns in patients with major depressive disorder (MDD) and investigate the connection between aberrant fALFF and clinical characteristics. Methods: This study included 35 MDD patients with GI symptoms (GI-MDD patients), 17 MDD patients without GI symptoms (nGI-MDD patients), and 28 healthy controls (HCs). The fALFF method was used to analyze the resting-state functional magnetic resonance imaging data. Correlation analysis and pattern classification were employed to investigate the relationship of the fALFF patterns with the clinical characteristics of patients. Results: GI-MDD patients exhibited higher scores in the HRSD-17 and suffered more severe insomnia, anxiety/somatization, and weight loss than nGI-MDD patients. GI-MDD patients showed higher fALFF in the right superior frontal gyrus (SFG)/middle frontal gyrus (MFG) and lower fALFF in the left superior medial prefrontal cortex (MPFC) compared with nGI-MDD patients. A combination of the fALFF values of these two clusters could be applied to discriminate GI-MDD patients from nGI-MDD patients, with accuracy, sensitivity, and specificity of 86.54, 94.29, and 70.59%, respectively. Conclusion: GI-MDD patients showed more severe depressive symptoms. Increased fALFF in the right SFG/MFG and decreased fALFF in the left superior MPFC might be distinctive neurobiological features of MDD patients with GI symptoms.

Disrupted Regional Homogeneity in Major Depressive Disorder With Gastrointestinal Symptoms at Rest.

Background: Gastrointestinal (GI) symptoms are prominent in patients with major depressive disorder (MDD). Previous studies have reported brain structural and functional changes in both MDD and digestive system diseases but it remains unclear whether MDD patients with GI symptoms have brain imaging changes. Methods: We recruited 35 MDD patients with GI symptoms, 17 MDD patients without GI symptoms and 28 age-, gender-, and education-matched healthy controls. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with regional homogeneity (ReHo). Results: The GI group showed higher total HRSD-17 scores, anxiety/somatization, weight loss, and sleep disturbance scores compared to the non-GI group. We found increased ReHo in the right inferior parietal gyrus (IPL), bilateral supplementary motor area (SMA), bilateral cerebellum Crus II, left inferior frontal gyrus (IFG), and bilateral superior medial frontal cortex (SMFC) and decreased ReHo in the right posterior cingulate cortex (PCC), bilateral cuneus, and left middle occipital gyrus (MOG) in patients with GI symptoms relative to the HCs. The GI group showed higher ReHo values in the bilateral precuneus than the non-GI group. Conclusion: MDD patients with GI symptoms showed a greater severity of symptoms than MDD patients without GI symptoms, particularly in terms of anxiety/somatization, weight loss, and sleep disturbances. Increased activity in the default-mode network might be associated with GI symptoms in MDD patients.

Abnormal Default-Mode Network Homogeneity in Melancholic and Nonmelancholic Major Depressive Disorder at Rest.

Background: Melancholic depression has been assumed as a severe type of major depressive disorder (MDD). We aimed to explore if there were some distinctive alterations in melancholic MDD and whether the alterations could be used to discriminate the melancholic MDD and nonmelancholic MDD. Methods: Thirty-one outpatients with melancholic MDD, thirty-three outpatients with nonmelancholic MDD, and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the network homogeneity (NH) and support vector machine (SVM) methods. Results: Both patient groups exhibited increased NH in the right PCC/precuneus and right angular gyrus and decreased NH in the right middle temporal gyrus compared with healthy controls. Compared with nonmelancholic patients and healthy controls, melancholic patients exhibited significantly increased NH in the bilateral superior medial frontal gyrus and decreased NH in the left inferior temporal gyrus. But merely for melancholic patients, the NH of the right middle temporal gyrus was negatively correlated with TEPS total and contextual anticipatory scores. SVM analysis showed that a combination of NH values in the left superior medial frontal gyrus and left inferior temporal gyrus could distinguish melancholic patients from nonmelancholic patients with accuracy, sensitivity, and specificity of 79.66% (47/59), 70.97% (22/31), and 89.29%(25/28), respectively. Conclusion: Our findings showed distinctive network homogeneity alterations in melancholic MDD which may be potential imaging markers to distinguish melancholic MDD and nonmelancholic MDD.

Disrupted Regional Homogeneity in Melancholic and Non-melancholic Major Depressive Disorder at Rest.

Background: Melancholic depression has been viewed as one severe subtype of major depressive disorder (MDD). However, it is unclear whether melancholic depression has distinct changes in brain imaging. We aimed to explore specific or distinctive alterations in melancholic MDD and whether the alterations could be used to separate melancholic MDD from non-melancholic MDD or healthy controls. Materials and Methods: Thirty-one outpatients with melancholic MDD and thirty-three outpatients with non-melancholic MDD and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the regional homogeneity (ReHo) and support vector machine (SVM) methods. Results: Melancholic MDD patients exhibited lower ReHo in the right superior occipital gyrus/middle occipital gyrus than non-melancholic MDD patients and healthy controls. Merely for non-melancholic MDD patients, decreased ReHo in the right middle frontal gyrus was negatively correlated with the total HRSD-17 scores. SVM analysis results showed that a combination of abnormal ReHo in the right fusiform gyrus/cerebellum Crus I and the right superior occipital gyrus/middle occipital gyrus exhibited the highest accuracy of 83.05% (49/59), with a sensitivity of 90.32% (28/31), and a specificity of 75.00% (21/28) for discriminating patients with melancholic MDD from patients with non-melancholic MDD. And a combination of abnormal ReHo in the right fusiform gyrus/cerebellum VI and left postcentral gyrus/precentral gyrus exhibited the highest accuracy of 98.41% (62/63), with a sensitivity of 96.77% (30/31), and a specificity of 100.00%(32/32) for separating patients with melancholic MDD from healthy controls. Conclusion: Our findings showed the distinctive ReHo pattern in patients with melancholic MDD and found brain area that may be associated with the pathophysiology of non-melancholic MDD. Potential imaging markers for discriminating melancholic MDD from non-melancholic MDD or healthy controls were reported.