Evaluating personalized circulating tumor DNA detection for early-stage lung cancer.

Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL). Whole exome profiling was conducted on 61 tumor tissue samples to identify tumor-specific variants, which were then used to design personalized assay MarRyDa® for ctDNA detection. DNA extracted from BAL fluid and plasma were genotyped using MarRyDa® platform. Our analysis showed that histological subtypes and disease stages had significant differences in ctDNA detection rate. Furthermore, we found that DNA purified from BAL supernatants contains the highest levels of ctDNA compared with BAL precipitates and plasma; therefore, utilizing BAL supernatants for tumor detection might provide additional benefits. Finally, we demonstrated that tumor cellularity played significant roles in the design of personalized ctDNA panel which eventually impacts ctDNA detection sensitivity. We suggest setting a flexible criteria for sample quality control and utilization of BAL might benefit more patients in clinics.

Realizing ambitions: A framework for iteratively assessing and communicating national decarbonization progress.

A growing number of governments are pledging to achieve net-zero greenhouse gas emissions by mid-century. Despite such ambitions, realized emissions reductions continue to fall alarmingly short of modeled energy transition pathways for achieving net-zero. This gap is largely a result of the difficulty of realistically modeling all the techno-economic and sociopolitical capabilities that are required to deliver actual emissions reductions. This limitation of models suggests the need for an energy-systems analytical framework that goes well beyond energy-system modeling in order to close the gap between ambition and reality. Toward that end, we propose the Emissions-Sustainability-Governance-Operation (ESGO) framework for structured assessment and transparent communication of national capabilities and realization. We illustrate the critical role of energy modeling in ESGO using recent net-zero modeling studies for the world's two largest emitters, China and the United States. This illustration leads to recommendations for improvements to energy-system modeling to enable more productive ESGO implementation.

Combined Metabolome and Transcriptome Analyses of Young, Mature, and Old Rhizome Tissues of Zingiber officinale Roscoe.

Ginger (Zingiber officinale Roscoe) is known for its unique pungent taste and useability in traditional Chinese medicine. The main compounds in ginger rhizome can be classified as gingerols, diarylheptanoids, and volatile oils. The composition and concentrations of the bioactive compounds in ginger rhizome might vary according to the age of the rhizome. In this regard, the knowledge on the transcriptomic signatures and accumulation of metabolites in young (Y), mature (M), and old (O) ginger rhizomes is scarce. This study used HiSeq Illumina Sequencing and UPLC-MS/MS analyses to delineate how the expression of key genes changes in Y, M, and O ginger rhizome tissues and how it affects the accumulation of metabolites in key pathways. The transcriptome sequencing identified 238,157 genes of which 13,976, 11,243, and 24,498 were differentially expressed (DEGs) in Y vs. M, M vs. O, and Y vs. O, respectively. These DEGs were significantly enriched in stilbenoid, diarylheptanoid, and gingerol biosynthesis, phenylpropanoid biosynthesis, plant-hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, and α-linoleic acid metabolism pathways. The metabolome profiling identified 661 metabolites of which 311, 386, and 296 metabolites were differentially accumulated in Y vs. M, Y vs. O, and M vs. O, respectively. These metabolites were also enriched in the pathways mentioned above. The DEGs and DAMs enrichment showed that the gingerol content is higher in Y rhizome, whereas the Y, M, and O tissues differ in linoleic and α-linoleic acid accumulation. Similarly, the starch and sucrose metabolism pathway is variably regulated in Y, M, and O rhizome tissues. Our results showed that ginger rhizome growth slows down (Y > M > O) probably due to changes in phytohormone signaling. Young ginger rhizome is the most transcriptionally and metabolically active tissue as compared to M and O. The transitioning from Y to M and O affects the gingerol, sugars, linoleic acid, and α-linoleic acid concentrations and related gene expressions.

Demands and countermeasures for outpatients and emergency patients during the outbreak of coronavirus disease 2019 in large general hospital. / 大型综合性医院2019å† çŠ¶ç— æ¯’ç— ç–«æƒ æœŸé—´é—¨æ€¥è¯Šæ‚£è€ å°±è¯Šéœ€æ±‚åŠåº”å¯¹.

OBJECTIVES: To discuss the demands and countermeasures for outpatients and emergency patients during the outbreak of coronavirus disease 2019 (COVID-19) in large general hospital. METHODS: By analyzing patients' demands, outpatient service system and emergency system complemented each other with the help of "internet medical" to provide online medical treatment, self-diagnosed pneumonia program, online pharmacies, outpatient appointment and online pre-examination services, open green channels for special patients, and to provide referral services for critical patients. The COVID-19 suspected patients and other common fever patients were separated from other patients. RESULTS: From January 28 to March 1, we have received 26 000 patients online, 1 856 special patients, 2 929 suspected patients and common fever patients including 31 confirmed patients, 0 case of misdiagnosis and cross-infection. CONCLUSIONS: Targeting patient's demands and taking appropriate measures are effective on meeting the needs of outpatients' and emergency patients' medical services.

Boundary-Induced Auxiliary Features in Scattering-Type Near-Field Fourier Transform Infrared Spectroscopy.

Phonon-polaritons (PhPs) in layered crystals, including hexagonal boron nitride (hBN), have been investigated by combined scattering-type scanning near-field optical microscopy (s-SNOM) and Fourier transform infrared (FTIR) spectroscopy. Nevertheless, many of such s-SNOM-based FTIR spectra features remain unexplored, especially those originated from the impact of boundaries. Here we observe real-space PhP propagations in thin-layer hBN sheets either supported or suspended by s-SNOM imaging. Then with a high-power broadband IR laser source, we identify two major peaks and multiple auxiliary peaks in the near-field amplitude spectra, obtained using scattering-type near-field FTIR spectroscopy, from both supported and suspended hBN. The major PhP propagation interference peak moves toward the major in-plane phonon peak when the IR illumination moves away from the hBN edge. Specific differences between the auxiliary peaks in the near-field amplitude spectra from supported and suspended hBN sheets are investigated regarding different boundary conditions, associated with edges and substrate interfaces. The outcomes may be explored in heterostructures for advanced nanophotonic applications.

[CLINICAL STUDY ON ZYGOMATIC SPINDLE-SHAPED OSTEOTOMY AND INTERNAL PUSH OF TITANIUM SCREW ANCHOR IN TREATMENT OF PROMINENT MALAR].

OBJECTIVE: To explore the effectiveness of the zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor for prominent malar. METHODS: Between July 2011 and January 2015, 58 patients with prominent malar underwent zygomatic spindle-shaped osteotomy and internal push of titanium screw anchor. There were 3 males and 55 females, aged 18-33 years (mean, 23 years). They had congenital bilateral prominent malar. Preoperative anteroposterior, lateral, supine position, 45" oblique photographs of the face were taken, three-dimensional CT reconstruction of face was performed. Simple prominent malar was observed in 30 cases, and prominent malar and zygomatic arch in 28 cases; zygomatic bone and zygomatic arch were symmetrical in 51 cases, and asymmetrical in 7 cases. RESULTS: All patients obtained stage I incision healing after operation, without infection or hematoma. Numbness of the upper lip occurred in 2 cases, limitation of mouth opening in 1 case, and nasolabial fold deepening in 1 case, which recovered spontaneously after 3 months. Fifty-eight cases were followed up 6-12 months (mean, 10 months). Zygomatic narrow spacing was 10.6-13.9 mm (mean, 11.2 mm). No ptosis of facial soft tissue, zygomatic step, facial nerve injury, raising eyebrow, dysfunction of eyes closure, or temporomandibular joint disorder syndrome occurred. Good bone healing was obtained, zygomatic facial sensation had no obvious abnormality, all patients were satisfied with the improvement of appearance. CONCLUSION: Zygomatic spindle-shaped osteotomy and internal push titanium screw anchor can effectively reduce the cheekbones, and maintain the natural curve of zygomatic body and zygomatic arch. Because of simple operation, less complications, and excellent results, it is an ideal plasty.

[Effects of AQP1 overexpression on morphology and water transport in mouse Schwann cells].

OBJECTIVE: To determine the effect of AQP1 gene on facial nerve edema following injury through investigation of the relationship between the expression of AQP1 gene and Schwann cells swelling. METHODS: The AQP1 expression in Schwann cells of mouse facial nerve tissues was detected by immunofluorescent staining. The transgenic protocol by lentivirus transduction was used to specifically upregulate AQP1 expression in Schwann cells. Lenti-AQP1 and CTRL (empty vector) transduced cells were observed during gene overexpression every 24 h for 6 days by using phase contrast microscopy. Cell volume of CTRL and Lenti-AQP1 treated cells was measured daily from the day of treatment, through day 6. RESULTS: Schwann cell primary cultures maintained a high level of AQP1 water channels, representing an ideal cell model to study the role of AQP1 in the facial nerve. The expression of AQP1 mRNA and protein in Schwann cells infected with the Lenti-AQP1 was increased significantly compared with CTRL lentivirus (P < 0.05). Lenti-AQP1 caused cell swelling in cultured Schwann cells, as validated by cell volume determinations (P < 0.01). CONCLUSIONS: AQP1 is an important factor responsible for the fast water transport of cultured Schwann cells. It plays an important role in facial nerve edema.

[Treatment of auricular keloids with surgery and intralesional injection of compound betamethasone].

OBJECTIVE: To investigate the treatment of auricular keloid with dinuclear surgery and intralesional injection of compound Betamethasone. METHODS: From Jan. 2008 to Jan. 2012, a total of 186 cases of ear keloid were treated by surgery only (22 cases), or intralesional injection of compound Betamethasone (34 cases), or combined dinuclear surgery with compound Betamethasone (130 cases). All the patients were followed up for one year. SPSS 16.0 software was used for statistical processing and analysis, and GraphPad inspection method for inspection. RESULTS: The effective rate was 54.55% (12/ 22) in surgery group and 55.88% (19/34)in injection group. The recurrence was obvious in injection group during the follow-up period. The effective rate was as high as 96.92% (126/130) in combined group with recurrence in 4 cases, which was significantly higher than that in other 2 groups (P < 0. 01). CONCLUSION: Combined dinuclear surgery and compound Betamethasone injection has a good therapeutic effect on auricular keloids.

A cryogenic scattering-type scanning near-field optical microscope.

Scattering-type scanning near-field optical microscopy (s-SNOM) provides few nanometer optical spatial resolution and is compatible with nearly any form of linear and nonlinear optical spectroscopy. We have developed a versatile s-SNOM instrument operating under cryogenic and variable temperature (∼20-500 K) and compatible with high magnetic fields (up to 7 T). The instrument features independent tip and sample scanning and free-space light delivery with an integrated off-axis parabolic mirror for tip-illumination and signal collection with a numerical aperture of N.A. = 0.45. The optics operate from the UV to THz range allowing for continuous wave, broadband, and ultrafast s-SNOM spectroscopy, including different variants of tip-enhanced spectroscopy. We discuss the instrument design, implementation, and demonstrate its performance with mid-infrared Drude response s-SNOM probing of the domain formation associated with the metal-insulator transitions of VO2 (TMIT ≃ 340 K) and V2O3 (TMIT ≃ 150 K). This instrument enables the study of mesoscopic order and domains of competing quantum phases in correlated electron materials over a wide range of controlled electric and magnetic fields, strain, current, and temperature.

[Topical application of leptin promotes burn wound healing in rats].

OBJECTIVE: To investigate the effect of topical application of leptin in promoting burn wound healing in rats. METHODS: Four parallel second-degree burn wounds induced on the back of 18 Wistar rats were divided into leptin treatment group (treated with topical application of 400 ng/ml leptin dissolved in PBS) and control group (treated with PBS). The time of wound healing was recorded, and the wound area that was not healed was measured at 3, 7, 11, 15, and 19 days after burns. The tissue at the peripheries of the wound was sampled at 7, 14 and 21 days after burns for pathological examination with HE staining and immunohistochemistry for proliferating cell nuclear antigen (PCNA) to evaluate the proliferation of keratinocytes. RESULTS: Compared with the control group, leptin-treated wounds showed a shorter time (by 2-3 days) of wound healing, and significant differences were found between the two groups in healing at 7, 11, 15, and 19 days after burns. HE staining and immunohistochemistry revealed a faster rate of epidermis growth and a greater thickness of the cuticular layer in leptin-treated wounds at 7, 14 and 21 days after burns. PCNA positivity in the keratinocytes was stronger in leptin-treated wounds than in the control wounds at 7 and 14 days, but no such distinct difference was noted at 21 days between the two groups. CONCLUSION: Topical application of leptin can promote re-epithelization in burn wounds to shorten the wound healing time of burns.

[Clinical application of three-dimensional reconstruction of CT images in treating mandibular angle hypertrophy].

OBJECTIVE: To investigate the clinical directive significance of three-dimensional reconstruction of CT in treating mandibular angle hypertrophy. METHODS: Between March 2009 and January 2011, 18 patients with mandibular angle hypertrophy were treated using the three-dimensional reconstruction technology of CT. All patients were female, aged 20-36 years with an average of 25 years. Eighteen patients included: 14 single mandibular angle hypertrophy, 3 mandibular angle hypertrophy with masseter hypertrophy, and 1 mandibular angle hypertrophy with bilateral asymmetry; 6 cases of ptosis of mandibular angle, 9 cases of prominent mandibular angle, and 3 cases of introversive mandibular angle. According to the types of mandibular angle hypertrophy, the surgical methods could be correctly chosen. The procedure was planned and simulated; the osteotomy line was marked and the osteotomy was measured on the workstations of three-dimensional reconstruction. RESULTS: No fracture of mandible occurred in the operation. Facial nerve temporary attack occurred in 1 case and recovered at 3 months after operation. All patients were followed up 6-12 months (mean, 7.6 months). After 6 months of operation, the effectiveness was satisfactory in 15 cases, basically satisfactory in 2 cases, and unsatisfactory in 1 case (bilateral asymmetry). CONCLUSION: Based on three-dimensional reconstruction technology of CT, surgical design performed on the model will promote the accuracy of operation. Basically symmetrical appearances can be achieved with satisfactory results.

Growth hormone pathway gene expression varies in porcine cumulus-oocyte complexes during in vitro maturation.

Growth hormone (GH) plays important roles in oocyte development and facilitates the successful production of competent oocytes in many species both in vivo and in vitro. However, the mechanism of GH action on oocyte maturation is not well known. In this paper, the temporospatial messenger ribonucleic acid expression patterns of GH and several other GH-related factors were quantitatively analyzed in porcine cumulus-oocytes complex throughout in vitro maturation (IVM). GH expression was decreased in oocytes during IVM while absent in cumulus cells. GH receptor, insulin-like growth factor-1 (IGF-1), and IGF-1 receptor expressions were also downregulated in oocytes. In cumulus cells, the expression of IGF-1 decreased significantly while IGF-1 receptor expression remained constant. The transcripts of Janus kinase 2 increased in both oocytes and cumulus cells during IVM. The current precise gene expression information provides further evidence to explain the complex network of GH signaling involved in IVM of porcine oocyte.

[Analysis of salt resistance on the poplar transferred with salt tolerance gene].

Poplar(Pupulus x Xiao zhannica, cv. "balizhuang-yang") transferred with mtl-D gene was used as an experimental material. Through tissue culture, aquaculture and pot culture transgenic poplars are tested with variant Nacl salt gradient. In it transgenic poplar raises its initial days for differentiation, differentiation rate, bud intensity, bud height and growth potential than control plant. At the same time, the transgenic poplar has higher rooting rate and more top roots, side roots and higher root length than control under the same salt stress. The result shows that the transgenic poplar has better tolerance ability than control plant in the salt 4@1000 contensity mediums.

GATA6 regulates differentiation of distal lung epithelium.

GATA6 is a member of the GATA family of zinc-finger transcriptional regulators and is the only known GATA factor expressed in the distal epithelium of the lung during development. To define the role that GATA6 plays during lung epithelial cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein in the distal lung epithelium of transgenic mice. Transgenic embryos lacked detectable alveolar epithelial type 1 cells in the distal airway epithelium. These embryos also exhibited increased Foxp2 gene expression, suggesting a disruption in late alveolar epithelial differentiation. Alveolar epithelial type 2 cells, which are progenitors of alveolar epithelial type 1 cells, were correctly specified as shown by normal thyroid transcription factor 1 and surfactant protein A gene expression. However, attenuated endogenous surfactant protein C expression indicated that alveolar epithelial type 2 cell differentiation was perturbed in transgenic embryos. The number of proximal airway tubules is also reduced in these embryos, suggesting a role for GATA6 in regulating distal-proximal airway development. Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter. Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse.

Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues.

In this study, we describe the isolation and characterization of Foxp4, a new member of the Foxp subfamily of winged-helix transcription factors. The full-length mouse Foxp4 cDNA encodes a 685-amino-acid protein that is similar to Foxp1 and Foxp2. Foxp4 gene expression is observed primarily in pulmonary, neural, and gut tissues during embryonic development. To compare the protein expression patterns of Foxp4 to Foxp1 and Foxp2, specific polyclonal antisera to each of these proteins was used in immunohistochemical analysis of mouse embryonic tissues. All three proteins are expressed in lung epithelium with Foxp1 and Foxp4 expressed in both proximal and distal airway epithelium while Foxp2 is expressed primarily in distal epithelium. Foxp1 protein expression is also observed in the mesenchyme and vascular endothelial cells of the lung. At embryonic day 12.5, Foxp1 and Foxp2 are expressed in both the mucosal and epithelial layers of the intestine. However, Foxp2 is expressed only in the outer mucosal layer of the intestine and stomach later in development. Finally, Foxp4 is expressed exclusively in the epithelial cells of the developing intestine, where, in late development, it is expressed in a gradient along the longitudinal axis of the villi.

Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues.

In this study, we describe the isolation and characterization of Foxp4, a new member of the Foxp subfamily of winged-helix transcription factors. The full-length mouse Foxp4 cDNA encodes a 685-amino-acid protein that is similar to Foxp1 and Foxp2. Foxp4 gene expression is observed primarily in pulmonary, neural, and gut tissues during embryonic development. To compare the protein expression patterns of Foxp4 to Foxp1 and Foxp2, specific polyclonal antisera to each of these proteins was used in immunohistochemical analysis of mouse embryonic tissues. All three proteins are expressed in lung epithelium with Foxp1 and Foxp4 expressed in both proximal and distal airway epithelium while Foxp2 is expressed primarily in distal epithelium. Foxp1 protein expression is also observed in the mesenchyme and vascular endothelial cells of the lung. At embryonic day 12.5, Foxp1 and Foxp2 are expressed in both the mucosal and epithelial layers of the intestine. However, Foxp2 is expressed only in the outer mucosal layer of the intestine and stomach later in development. Finally, Foxp4 is expressed exclusively in the epithelial cells of the developing intestine, where, in late development, it is expressed in a gradient along the longitudinal axis of the villi.